rs920314016

Variant names:

• chr19-497985-G-A
• NM_130760.3:c.205G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-497985-G-A
• chr19-497985-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130760.3(MADCAM1):​c.205G>A​(p.Ala69Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 1,346,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MADCAM1 NM_130760.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064605564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MADCAM1	NM_130760.3	c.205G>A	p.Ala69Thr	missense_variant	Exon 2 of 5	ENST00000215637.8	NP_570116.2
MADCAM1	NM_130762.3	c.205G>A	p.Ala69Thr	missense_variant	Exon 2 of 4		NP_570118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MADCAM1	ENST00000215637.8	c.205G>A	p.Ala69Thr	missense_variant	Exon 2 of 5	1	NM_130760.3	ENSP00000215637.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000223 AC: 3 AN: 1346366 Hom.: 0 Cov.: 32 AF XY: 0.00000301 AC XY: 2 AN XY: 663908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.0000178

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0085	.;T;T;T;.;T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.67	T;T;T;T;T;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.065	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;.;.;L;L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.82	.;.;.;.;N;N;.
REVEL	Benign	0.15
Sift	Benign	0.28	.;.;.;.;T;T;.
Sift4G	Benign	0.13	T;T;T;T;T;T;T
Polyphen		0.37	.;.;.;.;.;B;.
Vest4		0.063
MutPred		0.13		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.14
MPC		0.22
ClinPred		0.11	T
GERP RS		-3.4
Varity_R		0.26
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-497985;