rs2240953

Positions:

• chr9-128348613-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.086 (876 hom., cov: 32)
  • Exomes 𝑓: 0.053 (3169 hom.)
• Consequence: SLC27A4 NM_005094.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.14

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
SLC27A4	NM_005094.4	c.625G>A	p.Gly209Ser	missense_variant	4/13	ENST00000300456.5
SLC27A4	XM_047422664.1	c.658G>A	p.Gly220Ser	missense_variant	4/13
SLC27A4	XM_017014222.2	c.625G>A	p.Gly209Ser	missense_variant	5/14
SLC27A4	XM_024447391.2	c.625G>A	p.Gly209Ser	missense_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A4	ENST00000300456.5	c.625G>A	p.Gly209Ser	missense_variant	4/13	1	NM_005094.4	P1
SLC27A4	ENST00000372870.5	c.231+5332G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13144 AN: 152112 Hom.: 873 Cov.: 32

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

GnomAD3 exomes AF: 0.0753 AC: 18900 AN: 251064 Hom.: 1061 AF XY: 0.0708 AC XY: 9608 AN XY: 135722

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 SAS exome AF: 0.0911

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.: 33 AF XY: 0.0527 AC XY: 38314 AN XY: 727044

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0969

Gnomad4 ASJ exome AF: 0.0172

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.0875

Gnomad4 FIN exome AF: 0.0716

Gnomad4 NFE exome AF: 0.0388

Gnomad4 OTH exome AF: 0.0546

GnomAD4 genome AF: 0.0865 AC: 13166 AN: 152230 Hom.: 876 Cov.: 32 AF XY: 0.0893 AC XY: 6649 AN XY: 74422

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0940

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0370

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0473 Hom.: 613

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Dec 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.8
DANN	Benign	0.40
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.72	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.026
Sift	Benign	0.74	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.27
ClinPred		0.000013	T
GERP RS		0.64
Varity_R		0.026
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs2240953; hg19: chr9-131110892; COSMIC: COSV55959657;