rs17243407

Positions:

• chr5-7858008-G-A
• chr5-7858008-G-C

Variant summary

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

The XM_024446064.2(MTRR):​c.-133+1116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,160 control chromosomes in the GnomAD database, including 1,827 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 0.13 (1827 hom., cov: 32)
• Consequence: MTRR XM_024446064.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTRR	XM_024446064.2	c.-133+1116G>A		intron_variant
MTRR	XM_047417233.1	c.-452+1116G>A		intron_variant
MTRR	XM_047417234.1	c.-132-3943G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTRR	ENST00000502509.5	n.392-3943G>A		intron_variant, non_coding_transcript_variant		3
MTRR	ENST00000507837.5	n.506+1116G>A		intron_variant, non_coding_transcript_variant		4
MTRR	ENST00000511639.1	n.492+1116G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20403 AN: 152042 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.134 AC: 20406 AN: 152160 Hom.: 1827 Cov.: 32 AF XY: 0.132 AC XY: 9803 AN XY: 74370

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0846

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.110

Alfa AF: 0.178 Hom.: 3334

Bravo AF: 0.123

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.85
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17243407; hg19: chr5-7858121;