rs162032

Variant names:

• chr5-7880521-A-G
• rs162032
• NM_002454.3:c.780+2199A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-7880521-A-G
• chr5-7880521-A-T

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+2199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,188 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: 32)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTRR	NM_002454.3	c.780+2199A>G		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+2199A>G		intron_variant	Intron 5 of 14	1	NM_002454.3	ENSP00000402510.2

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128626 AN: 152068 Hom.: 54658 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.846 AC: 128749 AN: 152188 Hom.: 54716 Cov.: 32 AF XY: 0.844 AC XY: 62772 AN XY: 74378

African (AFR) AF: 0.910 AC: 37835 AN: 41562

American (AMR) AF: 0.851 AC: 13010 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2729 AN: 3464

East Asian (EAS) AF: 0.697 AC: 3600 AN: 5164

South Asian (SAS) AF: 0.803 AC: 3873 AN: 4822

European-Finnish (FIN) AF: 0.818 AC: 8659 AN: 10586

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56284 AN: 67978

Other (OTH) AF: 0.825 AC: 1745 AN: 2116

Alfa AF: 0.795 Hom.: 2687

Bravo AF: 0.849

Asia WGS AF: 0.750 AC: 2608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.94
DANN	Benign	0.43
PhyloP100		-1.8
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: rs162032; hg19: chr5-7880634;