19-501900-C-G

Variant names:

• chr19-501900-C-G
• rs3745925
• NM_130760.3:c.899C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130760.3(MADCAM1):​c.899C>G​(p.Pro300Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MADCAM1 NM_130760.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 24 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088134974).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MADCAM1	NM_130760.3	MANE Select	c.899C>G	p.Pro300Arg	missense	Exon 4 of 5	NP_570116.2
	MADCAM1	NM_130762.3		c.668-2845C>G		intron	N/A	NP_570118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MADCAM1	ENST00000215637.8	TSL:1 MANE Select	c.899C>G	p.Pro300Arg	missense	Exon 4 of 5	ENSP00000215637.2
	MADCAM1	ENST00000346144.8	TSL:1	c.668-2845C>G		intron	N/A	ENSP00000304247.2
	MADCAM1	ENST00000382683.8	TSL:1	c.383-2845C>G		intron	N/A	ENSP00000372130.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 158904 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394120 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 688256

African (AFR) AF: 0.0000319 AC: 1 AN: 31318

American (AMR) AF: 0.00 AC: 0 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23422

East Asian (EAS) AF: 0.00 AC: 0 AN: 36762

South Asian (SAS) AF: 0.00 AC: 0 AN: 77564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078956

Other (OTH) AF: 0.00 AC: 0 AN: 57454

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.20
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.031
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.53	T
Sift4G	Uncertain	0.058	T
Polyphen		0.96	P
Vest4		0.22
MutPred		0.29		Gain of MoRF binding (P = 0.0014)
MVP		0.21
MPC		0.70
ClinPred		0.19	T
GERP RS		-0.82
Varity_R		0.020
gMVP		0.30
Mutation Taster		=97/3	polymorphism

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: rs3745925; hg19: chr19-501900;