rs1801394

chr5-7870860-A-G

• Frequency:
  • Genomes: 𝑓 0.45 (16801 hom., cov: 34)
  • Exomes 𝑓: 0.47 (29891 hom.)
• Consequence: MTRR NM_002454 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:9 O:2
• Conservation: PhyloP100: 0.0980

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.4935942E-4).
• BP6: Variant 5:7870860-A>G is Benign according to our data. Variant chr5-7870860-A-G is described in ClinVar as [Benign]. Clinvar id is 7029. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-7870860-A-G is described in Lovd as [Benign].
• BA1: GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTRR	NM_002454.3	c.66A>G	p.Ile22Met	missense_variant	2/15	ENST00000440940.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTRR	ENST00000440940.7	c.66A>G	p.Ile22Met	missense_variant	2/15	1	NM_002454.3	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68524 AN: 152052 Hom.: 16801 Cov.: 34

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.430

GnomAD3 exomes AF: 0.466 AC: 117132 AN: 251460 Hom.: 29891 AF XY: 0.482 AC XY: 65443 AN XY: 135902

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.525

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.554

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.532 AC: 777894 AN: 1461798 Hom.: 212709 AF XY: 0.534 AC XY: 387990 AN XY: 727196

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.500

Alfa AF: 0.515 Hom.: 43514

Bravo AF: 0.421

TwinsUK AF: 0.553 AC: 2050

ALSPAC AF: 0.565 AC: 2179

ESP6500AA AF: 0.270 AC: 1188

ESP6500EA AF: 0.546 AC: 4696

ExAC AF: 0.473 AC: 57411

Asia WGS AF: 0.387 AC: 1347 AN: 3478

EpiCase AF: 0.529

EpiControl AF: 0.524

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:9Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK:

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, PreventionGenetics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Methylcobalamin deficiency type cblE Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 04, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Gastrointestinal stromal tumor Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Department of Pharmacy and Biotechnology, University of Bologna

-

- -

Disorders of Intracellular Cobalamin Metabolism Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Down syndrome, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2005

- -

Neural tube defects, folate-sensitive, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.32

T

BayesDel_noAF

Benign

-0.090

Cadd

Benign

23

Dann

Uncertain

0.99

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.10

N

LIST_S2

Uncertain

0.92

D;D;D;D;D

MetaRNN

Benign

0.00045

T;T;T;T;T

MetaSVM

Benign

-0.91

T

MutationAssessor

Uncertain

2.3

M;.;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.60

T

PROVEAN

Benign

-2.2

N;N;D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

D;D;D;T;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Vest4

0.26

MPC

0.32

ClinPred

0.049

T

GERP RS

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.37

gMVP

0.77

Splicing

Find out SpliceAI and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1801394; hg19: chr5-7870973; COSMIC: COSV52943975; COSMIC: COSV52943975;