rs162049

chr5-7893008-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002454.3(MTRR):c.1557+95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,360,854 control chromosomes in the GnomAD database, including 424,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48955 hom., cov: 34)
  • Exomes 𝑓: 0.79 (375457 hom.)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.84

Genes affected

MTRR (HGNC:7473): (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-7893008-G-A is Benign according to our data. Variant chr5-7893008-G-A is described in ClinVar as [Benign]. Clinvar id is 1230987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTRR	NM_002454.3	c.1557+95G>A		intron_variant		ENST00000440940.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTRR	ENST00000440940.7	c.1557+95G>A		intron_variant		1	NM_002454.3	P1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121284 AN: 152150 Hom.: 48904 Cov.: 34

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.785 AC: 948746 AN: 1208586 Hom.: 375457 Cov.: 17 AF XY: 0.784 AC XY: 473774 AN XY: 604466

Gnomad4 AFR exome AF: 0.877

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.763

Gnomad4 FIN exome AF: 0.748

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.779

GnomAD4 genome AF: 0.797 AC: 121401 AN: 152268 Hom.: 48955 Cov.: 34 AF XY: 0.793 AC XY: 58997 AN XY: 74442

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.781

Alfa AF: 0.793 Hom.: 43658

Bravo AF: 0.799

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.015
Dann	Benign	0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs162049; hg19: chr5-7893121;