rs326120

Positions:

• chr5-7874734-G-A
• chr5-7874734-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002454.3(MTRR):​c.284-524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 151,996 control chromosomes in the GnomAD database, including 54,716 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 0.85 (54716 hom., cov: 30)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRR	NM_002454.3	c.284-524G>A		intron_variant		ENST00000440940.7	NP_002445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTRR	ENST00000440940.7	c.284-524G>A		intron_variant		1	NM_002454.3	ENSP00000402510	P1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128612 AN: 151880 Hom.: 54659 Cov.: 30

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.847 AC: 128731 AN: 151996 Hom.: 54716 Cov.: 30 AF XY: 0.845 AC XY: 62777 AN XY: 74300

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.828

Alfa AF: 0.832 Hom.: 24043

Bravo AF: 0.848

Asia WGS AF: 0.753 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.40

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: rs326120; hg19: chr5-7874847;