rs7703033

Variant names:

• chr5-7879837-G-A
• rs7703033
• NM_002454.3:c.780+1515G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-7879837-G-A
• chr5-7879837-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002454.3(MTRR):​c.780+1515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,062 control chromosomes in the GnomAD database, including 6,188 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 0.28 (6188 hom., cov: 32)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87
• Publications: 11 publications found

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]

MTRR Gene-Disease associations (from GenCC):

• methylcobalamin deficiency type cblE

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTRR	NM_002454.3	c.780+1515G>A		intron_variant	Intron 5 of 14	ENST00000440940.7	NP_002445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTRR	ENST00000440940.7	c.780+1515G>A		intron_variant	Intron 5 of 14	1	NM_002454.3	ENSP00000402510.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42405 AN: 151944 Hom.: 6188 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.279 AC: 42408 AN: 152062 Hom.: 6188 Cov.: 32 AF XY: 0.279 AC XY: 20712 AN XY: 74324

African (AFR) AF: 0.236 AC: 9803 AN: 41460

American (AMR) AF: 0.226 AC: 3458 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3468

East Asian (EAS) AF: 0.187 AC: 967 AN: 5166

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4826

European-Finnish (FIN) AF: 0.349 AC: 3685 AN: 10548

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21559 AN: 67986

Other (OTH) AF: 0.265 AC: 561 AN: 2114

Alfa AF: 0.297 Hom.: 30250

Bravo AF: 0.266

Asia WGS AF: 0.173 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.74
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7703033; hg19: chr5-7879950;