Variant chr19-501900-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_130760.3(MADCAM1):c.899C>A(p.Pro300His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,545,340 control chromosomes in the GnomAD database, including 35,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3561 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32107 hom. )

Consequence

MADCAM1
NM_130760.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

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-AS1 (HGNC:55315): (MADCAM1 antisense RNA 1)

MADCAM1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029996634).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MADCAM1	NM_130760.3 linkuse as main transcript	c.899C>A	p.Pro300His	missense_variant	4/5	ENST00000215637.8	NP_570116.2
MADCAM1-AS1	XR_936221.4 linkuse as main transcript	n.515-276G>T		intron_variant, non_coding_transcript_variant
MADCAM1	NM_130762.3 linkuse as main transcript	c.668-2845C>A		intron_variant			NP_570118.1
MADCAM1-AS1	XR_007067073.1 linkuse as main transcript	n.515-276G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADCAM1	ENST00000215637.8 linkuse as main transcript	c.899C>A	p.Pro300His	missense_variant	4/5	1	NM_130760.3	ENSP00000215637	P2	Q13477-1
MADCAM1-AS1	ENST00000592413.2 linkuse as main transcript	n.459-276G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32471

AN:

151774

Hom.:

3562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.214

AC:

34007

AN:

158904

Hom.:

3814

AF XY:

0.209

AC XY:

17880

AN XY:

85562

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.212

AC:

295833

AN:

1393448

Hom.:

32107

Cov.:

AF XY:

0.210

AC XY:

144329

AN XY:

687900

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.214

AC:

32468

AN:

151892

Hom.:

3561

Cov.:

AF XY:

0.214

AC XY:

15895

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.333

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.209

Hom.:

6127

Bravo

AF:

0.213

TwinsUK

AF:

0.198

AC:

733

ALSPAC

AF:

0.210

AC:

809

ESP6500AA

AF:

0.200

AC:

870

ESP6500EA

AF:

0.201

AC:

1715

ExAC

AF:

0.162

AC:

18891

Asia WGS

AF:

0.204

AC:

711

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.18

DEOGEN2

Benign

0.025

T;.;T;T;T;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.51

T;T;T;T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;.;.;.;.;L;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

.;.;.;.;.;N;.

REVEL

Benign

0.15

Sift

Benign

0.58

.;.;.;.;.;T;.

Sift4G

Uncertain

0.021

D;D;D;D;D;D;D

Polyphen

1.0

.;.;.;.;.;D;.

Vest4

0.26

MPC

0.81

ClinPred

0.015

GERP RS

-0.82

Varity_R

0.039

gMVP

0.26

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