Variant 4-89909322-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001410735.1(MMRN1):c.-105T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,609,990 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 50 hom. )

Consequence

MMRN1
NM_001410735.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0700

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-89909322-T-C is Benign according to our data. Variant chr4-89909322-T-C is described in ClinVar as [Benign]. Clinvar id is 716819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2246/151586) while in subpopulation AFR AF= 0.0506 (2095/41440). AF 95% confidence interval is 0.0488. There are 68 homozygotes in gnomad4. There are 1007 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 68 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMRN1	NM_007351.3 link	c.670T>C	p.Leu224Leu	synonymous_variant	2/8	ENST00000264790.7	NP_031377.2	Q13201-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMRN1	ENST00000264790.7 link	c.670T>C	p.Leu224Leu	synonymous_variant	2/8	1	NM_007351.3	ENSP00000264790.2	Q13201-1
MMRN1	ENST00000508372 link	c.-105T>C		5_prime_UTR_premature_start_codon_gain_variant	2/8	2		ENSP00000426461.1	E7EPG1
MMRN1	ENST00000394980.5 link	c.670T>C	p.Leu224Leu	synonymous_variant	3/9	5		ENSP00000378431.1	Q13201-1
MMRN1	ENST00000508372 link	c.-105T>C		5_prime_UTR_variant	2/8	2		ENSP00000426461.1	E7EPG1

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2240

AN:

151468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.00387

AC:

968

AN:

249992

Hom.:

AF XY:

0.00283

AC XY:

383

AN XY:

135142

show subpopulations

Gnomad AFR exome

AF:

0.0528

Gnomad AMR exome

AF:

0.00268

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00143

AC:

2081

AN:

1458404

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

898

AN XY:

725550

show subpopulations

Gnomad4 AFR exome

AF:

0.0491

Gnomad4 AMR exome

AF:

0.00303

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000703

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.0148

AC:

2246

AN:

151586

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1007

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.0506

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0129

Alfa

AF:

0.00651

Hom.:

Bravo

AF:

0.0165

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000547

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.3

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over