rs2240953

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005094.4(SLC27A4):c.625G>A(p.Gly209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,613,692 control chromosomes in the GnomAD database, including 4,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 876 hom., cov: 32)

Exomes 𝑓: 0.053 ( 3169 hom. )

Consequence

SLC27A4
NM_005094.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.14

Publications

29 publications found

Variant links:

Genes affected

SLC27A4 (HGNC:10998): (solute carrier family 27 member 4) This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]

SLC27A4 Gene-Disease associations (from GenCC):

ichthyosis prematurity syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, G2P

SLC27A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012699962).

BP6

Variant 9-128348613-G-A is Benign according to our data. Variant chr9-128348613-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1331386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A4	NM_005094.4 link	c.625G>A	p.Gly209Ser	missense_variant	Exon 4 of 13	ENST00000300456.5	NP_005085.2	Q6P1M0-1A0A024R8D2
SLC27A4	XM_047422664.1 link	c.658G>A	p.Gly220Ser	missense_variant	Exon 4 of 13		XP_047278620.1
SLC27A4	XM_017014222.2 link	c.625G>A	p.Gly209Ser	missense_variant	Exon 5 of 14		XP_016869711.1	Q6P1M0-1A0A024R8D2
SLC27A4	XM_024447391.2 link	c.625G>A	p.Gly209Ser	missense_variant	Exon 5 of 14		XP_024303159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC27A4	ENST00000300456.5 link	c.625G>A	p.Gly209Ser	missense_variant	Exon 4 of 13	1	NM_005094.4	ENSP00000300456.3		Q6P1M0-1
SLC27A4	ENST00000372870.5 link	c.231+5332G>A		intron_variant	Intron 2 of 5	1		ENSP00000361961.1		Q6P1M0-2

Frequencies

GnomAD3 genomes

AF:

0.0864

AC:

13144

AN:

152112

Hom.:

873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0760

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.0941

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0370

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0753

AC:

18900

AN:

251064

AF XY:

0.0708

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.0803

Gnomad NFE exome

AF:

0.0370

Gnomad OTH exome

AF:

0.0508

GnomAD4 exome

AF:

0.0526

AC:

76941

AN:

1461462

Hom.:

3169

Cov.:

AF XY:

0.0527

AC XY:

38314

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.168

AC:

5621

AN:

33480

American (AMR)

AF:

0.0969

AC:

4334

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

450

AN:

26136

East Asian (EAS)

AF:

0.217

AC:

8624

AN:

39700

South Asian (SAS)

AF:

0.0875

AC:

7545

AN:

86254

European-Finnish (FIN)

AF:

0.0716

AC:

3797

AN:

53022

Middle Eastern (MID)

AF:

0.0187

AC:

108

AN:

5768

European-Non Finnish (NFE)

AF:

0.0388

AC:

43166

AN:

1111986

Other (OTH)

AF:

0.0546

AC:

3296

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4423

8846

13269

17692

22115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1908

3816

5724

7632

9540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0865

AC:

13166

AN:

152230

Hom.:

876

Cov.:

AF XY:

0.0893

AC XY:

6649

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.168

AC:

6957

AN:

41532

American (AMR)

AF:

0.0762

AC:

1167

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3472

East Asian (EAS)

AF:

0.193

AC:

995

AN:

5158

South Asian (SAS)

AF:

0.0940

AC:

453

AN:

4820

European-Finnish (FIN)

AF:

0.0774

AC:

821

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0370

AC:

2515

AN:

68014

Other (OTH)

AF:

0.0691

AC:

146

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

609

1218

1828

2437

3046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0540

Hom.:

1378

Bravo

AF:

0.0909

TwinsUK

AF:

0.0437

AC:

162

ALSPAC

AF:

0.0441

AC:

170

ESP6500AA

AF:

0.172

AC:

757

ESP6500EA

AF:

0.0371

AC:

319

ExAC

AF:

0.0750

AC:

9103

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.8

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.051

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.72

PhyloP100

1.1

PrimateAI

Benign

0.25

PROVEAN

Benign

1.8

REVEL

Benign

0.026

Sift

Benign

0.74

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.031

MPC

0.27

ClinPred

0.000013

GERP RS

0.64

Varity_R

0.026

gMVP

0.17

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over