dbSNP rs367987587: BTC:p.Val85Leu (chr4-74755887-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001729.4(BTC):c.253G>T(p.Val85Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V85M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BTC
NM_001729.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Variant links:

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]

BTC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18172807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTC	NM_001729.4 link	c.253G>T	p.Val85Leu	missense_variant	Exon 3 of 6	ENST00000395743.8	NP_001720.1	P35070A0A0S2Z437
BTC	NM_001316963.2 link	c.253G>T	p.Val85Leu	missense_variant	Exon 3 of 5		NP_001303892.1	P35070A0A0S2Z3I5
BTC	XM_011532211.2 link	c.253G>T	p.Val85Leu	missense_variant	Exon 3 of 6		XP_011530513.1	P35070A0A0S2Z437
BTC	XM_047416103.1 link	c.253G>T	p.Val85Leu	missense_variant	Exon 3 of 5		XP_047272059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTC	ENST00000395743.8 link	c.253G>T	p.Val85Leu	missense_variant	Exon 3 of 6	1	NM_001729.4	ENSP00000379092.3		P35070
BTC	ENST00000512743.1 link	c.187G>T	p.Val63Leu	missense_variant	Exon 2 of 4	5		ENSP00000421747.1		H0Y8Q5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.27

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.81

M_CAP

Benign

0.0088

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.75

REVEL

Benign

0.097

Sift

Benign

0.82

Sift4G

Benign

0.42

Polyphen

0.42

Vest4

0.32

MutPred

0.54

Gain of glycosylation at T90 (P = 0.0436);

MVP

0.58

MPC

0.031

ClinPred

0.49

GERP RS

3.8

Varity_R

0.095

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over