chr4-89949208-G-A

Variant names:

• chr4-89949208-G-A
• rs3775483
• NM_007351.3:c.3119-2397G>A

Variant summary

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

The NM_007351.3(MMRN1):​c.3119-2397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,046 control chromosomes in the GnomAD database, including 30,320 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 0.63 (30320 hom., cov: 32)
• Consequence: MMRN1 NM_007351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 4 publications found

Genes affected

MMRN1 (HGNC:7178): (multimerin 1) Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. It is comprised of subunits linked by interchain disulfide bonds to form large, variably sized homomultimers. Multimerin is a factor V/Va-binding protein and may function as a carrier protein for platelet factor V. It may also have functions as an extracellular matrix or adhesive protein. Recently, patients with an unusual autosomal-dominant bleeding disorder (factor V Quebec) were found to have a deficiency of platelet multimerin. [provided by RefSeq, Jul 2008]

MMRN1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007351.3. 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
	MMRN1	NM_007351.3	MANE Select	c.3119-2397G>A		intron	N/A	NP_031377.2
	MMRN1	NM_001371403.1		c.3119-2397G>A		intron	N/A	NP_001358332.1	Q13201-1
	MMRN1	NM_001410735.1		c.2345-2397G>A		intron	N/A	NP_001397664.1	E7EPG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMRN1	ENST00000264790.7	TSL:1 MANE Select	c.3119-2397G>A		intron	N/A	ENSP00000264790.2	Q13201-1
	MMRN1	ENST00000394980.5	TSL:5	c.3119-2397G>A		intron	N/A	ENSP00000378431.1	Q13201-1
	MMRN1	ENST00000955234.1		c.3116-2397G>A		intron	N/A	ENSP00000625293.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95608 AN: 151928 Hom.: 30297 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.629 AC: 95676 AN: 152046 Hom.: 30320 Cov.: 32 AF XY: 0.634 AC XY: 47114 AN XY: 74314

African (AFR) AF: 0.651 AC: 27011 AN: 41466

American (AMR) AF: 0.591 AC: 9029 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3472

East Asian (EAS) AF: 0.881 AC: 4565 AN: 5180

South Asian (SAS) AF: 0.689 AC: 3324 AN: 4822

European-Finnish (FIN) AF: 0.668 AC: 7057 AN: 10558

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40560 AN: 67950

Other (OTH) AF: 0.618 AC: 1303 AN: 2110

Alfa AF: 0.598 Hom.: 34992

Bravo AF: 0.624

Asia WGS AF: 0.770 AC: 2675 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.79
DANN	Benign	0.57
PhyloP100		-0.098
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: rs3775483; hg19: chr4-90870359; COSMIC: COSV53338152; COSMIC: COSV53338152;