rs758502

Positions:

• chr19-495600-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000592413.2(MADCAM1-AS1):​n.543-5247G>A variant causes a intron, non coding transcript 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-AS1 ENST00000592413.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADCAM1-AS1	ENST00000592413.2	n.543-5247G>A		intron_variant, non_coding_transcript_variant		5
MADCAM1	ENST00000587541.5	c.10+5561C>T		intron_variant		2		ENSP00000475575

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

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.306

Alfa AF: 0.319 Hom.: 4167

Bravo AF: 0.306

Asia WGS AF: 0.235 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs758502; hg19: chr19-495600;