9-128348613-G-A

Variant names:

• chr9-128348613-G-A
• rs2240953
• NM_005094.4:c.625G>A

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.14
• Publications: 29 publications found

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005094.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A4	NM_005094.4	MANE Select	c.625G>A	p.Gly209Ser	missense	Exon 4 of 13	NP_005085.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A4	ENST00000300456.5	TSL:1 MANE Select	c.625G>A	p.Gly209Ser	missense	Exon 4 of 13	ENSP00000300456.3	Q6P1M0-1
	SLC27A4	ENST00000372870.5	TSL:1	c.231+5332G>A		intron	N/A	ENSP00000361961.1	Q6P1M0-2
	SLC27A4	ENST00000875280.1		c.625G>A	p.Gly209Ser	missense	Exon 4 of 13	ENSP00000545339.1

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

GnomAD2 exomes AF: 0.0753 AC: 18900 AN: 251064 AF XY: 0.0708

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

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

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

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: 69 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: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0370 AC: 2515 AN: 68014

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.1
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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