rs3775478

Variant names:

• chr4-89921689-A-G
• rs3775478
• NM_007351.3:c.851-1479A>G

Variant summary

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

The NM_007351.3(MMRN1):​c.851-1479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,188 control chromosomes in the GnomAD database, including 2,309 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 0.14 (2309 hom., cov: 32)
• Consequence: MMRN1 NM_007351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMRN1	NM_007351.3	c.851-1479A>G		intron_variant	Intron 3 of 7	ENST00000264790.7	NP_031377.2
MMRN1	NM_001371403.1	c.851-1479A>G		intron_variant	Intron 4 of 8		NP_001358332.1
MMRN1	NM_001410735.1	c.77-1479A>G		intron_variant	Intron 3 of 7		NP_001397664.1
MMRN1	XM_047449831.1	c.851-6106A>G		intron_variant	Intron 4 of 7		XP_047305787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMRN1	ENST00000264790.7	c.851-1479A>G		intron_variant	Intron 3 of 7	1	NM_007351.3	ENSP00000264790.2
MMRN1	ENST00000394980.5	c.851-1479A>G		intron_variant	Intron 4 of 8	5		ENSP00000378431.1
MMRN1	ENST00000508372.1	c.77-1479A>G		intron_variant	Intron 3 of 7	2		ENSP00000426461.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21873 AN: 152070 Hom.: 2302 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.144 AC: 21915 AN: 152188 Hom.: 2309 Cov.: 32 AF XY: 0.141 AC XY: 10513 AN XY: 74424

African (AFR) AF: 0.283 AC: 11739 AN: 41476

American (AMR) AF: 0.0873 AC: 1334 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1534 AN: 5186

South Asian (SAS) AF: 0.104 AC: 503 AN: 4830

European-Finnish (FIN) AF: 0.0772 AC: 820 AN: 10616

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0760 AC: 5170 AN: 68012

Other (OTH) AF: 0.153 AC: 323 AN: 2112

Alfa AF: 0.100 Hom.: 4757

Bravo AF: 0.152

Asia WGS AF: 0.206 AC: 714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.55
PhyloP100		-1.1
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: rs3775478; hg19: chr4-90842840;