4-74761295-G-T

Position:

• chr4-74761295-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001729.4(BTC):​c.164-5319C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,942 control chromosomes in the GnomAD database, including 28,291 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 0.61 (28291 hom., cov: 32)
• Consequence: BTC NM_001729.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

Genes affected

BTC (HGNC:1121): (betacellulin) This gene encodes a member of the epidermal growth factor (EGF) family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the secreted growth factor. A secreted form and a membrane-anchored form of this protein bind to multiple different EGF receptors. This protein promotes pancreatic cell proliferation and insulin secretion, as well as retinal vascular permeability. Mutations in this gene may be associated with type 2 diabetes in human patients. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTC	NM_001729.4	c.164-5319C>A		intron_variant		ENST00000395743.8
BTC	NM_001316963.2	c.164-5319C>A		intron_variant
BTC	XM_011532211.2	c.164-5319C>A		intron_variant
BTC	XM_047416103.1	c.164-5319C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTC	ENST00000395743.8	c.164-5319C>A		intron_variant		1	NM_001729.4	P1
BTC	ENST00000512743.1	c.100-5319C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92420 AN: 151824 Hom.: 28256 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.609 AC: 92515 AN: 151942 Hom.: 28291 Cov.: 32 AF XY: 0.608 AC XY: 45150 AN XY: 74242

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.608

Alfa AF: 0.622 Hom.: 4973

Bravo AF: 0.612

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.48

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: rs6840306; hg19: chr4-75686505;