rs3775478

chr4-89921689-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MMRN1	NM_007351.3	c.851-1479A>G		intron_variant		ENST00000264790.7
MMRN1	NM_001371403.1	c.851-1479A>G		intron_variant
MMRN1	NM_001410735.1	c.77-1479A>G		intron_variant
MMRN1	XM_047449831.1	c.851-6106A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMRN1	ENST00000264790.7	c.851-1479A>G		intron_variant		1	NM_007351.3	P1
MMRN1	ENST00000394980.5	c.851-1479A>G		intron_variant		5		P1
MMRN1	ENST00000508372.1	c.77-1479A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0760

Gnomad4 OTH AF: 0.153

Alfa AF: 0.0910 Hom.: 1619

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

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

LitVar

Other links and lift over

dbSNP: rs3775478; hg19: chr4-90842840;