chr19-498524-A-G

Variant names:

• chr19-498524-A-G
• rs2302217
• NM_130760.3:c.366A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.48
• Publications: 19 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130760.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MADCAM1	NM_130760.3	MANE Select	c.366A>G	p.Pro122Pro	synonymous	Exon 3 of 5	NP_570116.2	Q13477-1
	MADCAM1	NM_130762.3		c.366A>G	p.Pro122Pro	synonymous	Exon 3 of 4	NP_570118.1	Q13477-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MADCAM1	ENST00000215637.8	TSL:1 MANE Select	c.366A>G	p.Pro122Pro	synonymous	Exon 3 of 5	ENSP00000215637.2	Q13477-1
	MADCAM1	ENST00000346144.8	TSL:1	c.366A>G	p.Pro122Pro	synonymous	Exon 3 of 4	ENSP00000304247.2	Q13477-3
	MADCAM1	ENST00000382683.8	TSL:1	c.81A>G	p.Pro27Pro	synonymous	Exon 2 of 3	ENSP00000372130.4	Q13477-4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84905 AN: 151974 Hom.: 25230 Cov.: 34

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

GnomAD2 exomes AF: 0.513 AC: 65757 AN: 128096 AF XY: 0.505

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 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.: 52 AF XY: 0.475 AC XY: 304603 AN XY: 640760

African (AFR) AF: 0.777 AC: 20411 AN: 26268

American (AMR) AF: 0.457 AC: 9840 AN: 21548

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 8713 AN: 18600

East Asian (EAS) AF: 0.761 AC: 24582 AN: 32298

South Asian (SAS) AF: 0.532 AC: 32804 AN: 61698

European-Finnish (FIN) AF: 0.476 AC: 22497 AN: 47288

Middle Eastern (MID) AF: 0.473 AC: 2457 AN: 5194

European-Non Finnish (NFE) AF: 0.456 AC: 476250 AN: 1044408

Other (OTH) AF: 0.501 AC: 26936 AN: 53784

GnomAD4 genome AF: 0.559 AC: 85005 AN: 152092 Hom.: 25273 Cov.: 34 AF XY: 0.558 AC XY: 41469 AN XY: 74332

African (AFR) AF: 0.762 AC: 31631 AN: 41532

American (AMR) AF: 0.476 AC: 7283 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3881 AN: 5148

South Asian (SAS) AF: 0.543 AC: 2620 AN: 4822

European-Finnish (FIN) AF: 0.484 AC: 5125 AN: 10578

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31113 AN: 67936

Other (OTH) AF: 0.533 AC: 1122 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.46
PhyloP100		-6.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2302217; hg19: chr19-498524; COSMIC: COSV53129843;