rs162048

Variant names:

• chr5-7892197-G-A
• rs162048
• NM_002454.3:c.1371-530G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-7892197-G-A
• chr5-7892197-G-C
• chr5-7892197-G-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.1371-530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,182 control chromosomes in the GnomAD database, including 54,143 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 0.84 (54143 hom., cov: 32)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 13 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: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

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 (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002454.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRR	NM_002454.3	MANE Select	c.1371-530G>A		intron	N/A	NP_002445.2	Q9UBK8-2
	MTRR	NM_001364440.2		c.1371-530G>A		intron	N/A	NP_001351369.1	Q9UBK8-2
	MTRR	NM_001364441.2		c.1371-530G>A		intron	N/A	NP_001351370.1	Q9UBK8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRR	ENST00000440940.7	TSL:1 MANE Select	c.1371-530G>A		intron	N/A	ENSP00000402510.2	Q9UBK8-2
	MTRR	ENST00000264668.6	TSL:1	c.1452-530G>A		intron	N/A	ENSP00000264668.2	Q9UBK8-1
	MTRR	ENST00000513439.5	TSL:1	n.*1078-530G>A		intron	N/A	ENSP00000426710.1	D6RF21

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127960 AN: 152064 Hom.: 54089 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.842 AC: 128079 AN: 152182 Hom.: 54143 Cov.: 32 AF XY: 0.840 AC XY: 62476 AN XY: 74398

African (AFR) AF: 0.897 AC: 37266 AN: 41542

American (AMR) AF: 0.849 AC: 12994 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2728 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3473 AN: 5168

South Asian (SAS) AF: 0.803 AC: 3871 AN: 4818

European-Finnish (FIN) AF: 0.818 AC: 8665 AN: 10592

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56330 AN: 67978

Other (OTH) AF: 0.825 AC: 1740 AN: 2110

Alfa AF: 0.839 Hom.: 40422

Bravo AF: 0.843

Asia WGS AF: 0.742 AC: 2583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.83
PhyloP100		-0.45
Mutation Taster		=97/3	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: rs162048; hg19: chr5-7892310;