Variant 19-498524-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_130760.3(MADCAM1):c.366A>G(p.Pro122Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,463,178 control chromosomes in the GnomAD database, including 177,337 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 0.56 ( 25273 hom., cov: 34)

Exomes 𝑓: 0.48 ( 152064 hom. )

Consequence

MADCAM1
NM_130760.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.48

Variant links:

Genes affected

MADCAM1 (HGNC:6765): (mucosal vascular addressin cell adhesion molecule 1) The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4beta7), L-selectin, and VLA-4 (alpha4beta1) on myeloid cells to direct leukocytes into mucosal and inflamed tissues. It is a member of the immunoglobulin family and is similar to ICAM1 and VCAM1. At least seven alternatively spliced transcripts encoding different protein isoforms have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

MADCAM1 links:

MADCAM1 (HGNC:):

MADCAM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP7

Synonymous conserved (PhyloP=-6.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADCAM1	NM_130760.3 linkuse as main transcript	c.366A>G	p.Pro122Pro	synonymous_variant	3/5	ENST00000215637.8	NP_570116.2	Q13477-1
MADCAM1	NM_130762.3 linkuse as main transcript	c.366A>G	p.Pro122Pro	synonymous_variant	3/4		NP_570118.1	Q13477-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADCAM1	ENST00000215637.8 linkuse as main transcript	c.366A>G	p.Pro122Pro	synonymous_variant	3/5	1	NM_130760.3	ENSP00000215637.2		Q13477-1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84905

AN:

151974

Hom.:

25230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.761

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.513

AC:

65757

AN:

128096

Hom.:

17670

AF XY:

0.505

AC XY:

35205

AN XY:

69646

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.476

AC:

624490

AN:

1311086

Hom.:

152064

Cov.:

AF XY:

0.475

AC XY:

304603

AN XY:

640760

show subpopulations

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.761

Gnomad4 SAS exome

AF:

0.532

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.501

GnomAD4 genome

AF:

0.559

AC:

85005

AN:

152092

Hom.:

25273

Cov.:

AF XY:

0.558

AC XY:

41469

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.762

Gnomad4 AMR

AF:

0.476

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.754

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.458

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.411

Hom.:

2065

Bravo

AF:

0.569

Asia WGS

AF:

0.656

AC:

2283

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.24

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over