rs77153426

Variant names:

• chr6-122783744-G-A
• rs77153426
• NM_001446.5:c.376G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-122783744-G-A
• chr6-122783744-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001446.5(FABP7):​c.376G>A​(p.Val126Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000641 in 1,607,494 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (1 hom.)
• Consequence: FABP7 NM_001446.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 6 publications found

Genes affected

FABP7 (HGNC:3562): (fatty acid binding protein 7) The gene encodes a small, highly conserved cytoplasmic protein that bind long-chain fatty acids and other hydrophobic ligands. The encoded protein is important in the establishment of the radial glial fiber in the developing brain. Alternative splicing and promoter usage results in multiple transcript variants encoding different isoforms. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Jan 2016]

ENSG00000294893 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14036414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP7	NM_001446.5	c.376G>A	p.Val126Ile	missense_variant	Exon 4 of 4	ENST00000368444.8	NP_001437.1
FABP7	NM_001319042.2	c.364G>A	p.Val122Ile	missense_variant	Exon 4 of 4		NP_001305971.1
FABP7	NM_001319041.2	c.*3233G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001305970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000368444.8	c.376G>A	p.Val126Ile	missense_variant	Exon 4 of 4	1	NM_001446.5	ENSP00000357429.3
ENSG00000294893	ENST00000726593.1	n.331-2407C>T		intron_variant	Intron 1 of 1
ENSG00000294893	ENST00000726594.1	n.315-2407C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000778 AC: 19 AN: 244282 AF XY: 0.000106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000632 AC: 92 AN: 1455212 Hom.: 1 Cov.: 31 AF XY: 0.0000746 AC XY: 54 AN XY: 723784

African (AFR) AF: 0.00 AC: 0 AN: 33022

American (AMR) AF: 0.0000233 AC: 1 AN: 42952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.000178 AC: 15 AN: 84472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5752

European-Non Finnish (NFE) AF: 0.0000640 AC: 71 AN: 1110084

Other (OTH) AF: 0.0000332 AC: 2 AN: 60164

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000906 AC: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.10
Sift	Benign	0.062	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.55		Gain of methylation at K131 (P = 0.0758);
MVP		0.39
MPC		0.17
ClinPred		0.069	T
GERP RS		3.6
Varity_R		0.21
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs77153426; hg19: chr6-123104889;