rs758502

Variant names:

• chr19-495600-C-T
• rs758502
• ENST00000587541.5:c.10+5561C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000587541.5(MADCAM1):​c.10+5561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,066 control chromosomes in the GnomAD database, including 7,353 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 0.31 (7353 hom., cov: 32)
• Consequence: MADCAM1 ENST00000587541.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000587541.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MADCAM1	ENST00000587541.5	TSL:2	c.10+5561C>T		intron	N/A	ENSP00000475575.1	U3KQ59
	MADCAM1-AS1	ENST00000592413.2	TSL:5	n.543-5247G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46865 AN: 151948 Hom.: 7354 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.308 AC: 46881 AN: 152066 Hom.: 7353 Cov.: 32 AF XY: 0.306 AC XY: 22713 AN XY: 74344

African (AFR) AF: 0.284 AC: 11784 AN: 41482

American (AMR) AF: 0.279 AC: 4265 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1790 AN: 5176

South Asian (SAS) AF: 0.149 AC: 721 AN: 4826

European-Finnish (FIN) AF: 0.356 AC: 3760 AN: 10570

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22258 AN: 67930

Other (OTH) AF: 0.306 AC: 644 AN: 2108

Alfa AF: 0.319 Hom.: 5023

Bravo AF: 0.306

Asia WGS AF: 0.235 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs758502; hg19: chr19-495600;