chr5-151506958-A-G

Variant names:

• chr5-151506958-A-G
• rs7722485
• NM_001447.3:c.12517+196T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001447.3(FAT2):​c.12517+196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,164 control chromosomes in the GnomAD database, including 33,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (33007 hom., cov: 33)
• Consequence: FAT2 NM_001447.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 publications found

Genes affected

FAT2 (HGNC:3596): (FAT atypical cadherin 2) This gene is the second identified human homolog of the Drosophila fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development. The gene product is a member of the cadherin superfamily, a group of integral membrane proteins characterized by the presence of cadherin-type repeats. In addition to containing 34 tandem cadherin-type repeats, the gene product has two epidermal growth factor (EGF)-like repeats and one laminin G domain. This protein most likely functions as a cell adhesion molecule, controlling cell proliferation and playing an important role in cerebellum development. [provided by RefSeq, Jul 2008]

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT2	NM_001447.3	c.12517+196T>C		intron_variant	Intron 23 of 23	ENST00000261800.6	NP_001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT2	ENST00000261800.6	c.12517+196T>C		intron_variant	Intron 23 of 23	1	NM_001447.3	ENSP00000261800.5
FAT2	ENST00000520200.5	c.2833+196T>C		intron_variant	Intron 10 of 10	1		ENSP00000429678.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95820 AN: 152046 Hom.: 33005 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.653

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.630 AC: 95854 AN: 152164 Hom.: 33007 Cov.: 33 AF XY: 0.638 AC XY: 47418 AN XY: 74378

African (AFR) AF: 0.323 AC: 13394 AN: 41498

American (AMR) AF: 0.733 AC: 11212 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4354 AN: 5172

South Asian (SAS) AF: 0.851 AC: 4106 AN: 4826

European-Finnish (FIN) AF: 0.725 AC: 7680 AN: 10588

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50035 AN: 68000

Other (OTH) AF: 0.651 AC: 1377 AN: 2116

Alfa AF: 0.686 Hom.: 10780

Bravo AF: 0.616

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		0.0
Mutation Taster		=100/0	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: rs7722485; hg19: chr5-150886519; COSMIC: COSV55816004; COSMIC: COSV55816004;