rs4859417

Positions:

• chr4-74757951-T-C
• chr4-74757951-T-G

Variant summary

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

The ENST00000395743.8(BTC):​c.164-1975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,008 control chromosomes in the GnomAD database, including 16,557 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 0.46 (16557 hom., cov: 32)
• Consequence: BTC ENST00000395743.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTC	NM_001729.4	c.164-1975A>G		intron_variant		ENST00000395743.8	NP_001720.1
BTC	NM_001316963.2	c.164-1975A>G		intron_variant			NP_001303892.1
BTC	XM_011532211.2	c.164-1975A>G		intron_variant			XP_011530513.1
BTC	XM_047416103.1	c.164-1975A>G		intron_variant			XP_047272059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTC	ENST00000395743.8	c.164-1975A>G		intron_variant		1	NM_001729.4	ENSP00000379092	P1
BTC	ENST00000512743.1	c.100-1975A>G		intron_variant		5		ENSP00000421747

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70031 AN: 151888 Hom.: 16520 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.461 AC: 70126 AN: 152008 Hom.: 16557 Cov.: 32 AF XY: 0.463 AC XY: 34392 AN XY: 74280

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.412

Alfa AF: 0.429 Hom.: 6743

Bravo AF: 0.467

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.49

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: rs4859417; hg19: chr4-75683161;