1-11802721-A-G

Position:

• chr1-11802721-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005957.5(MTHFR):​c.236+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,172 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1508 hom., cov: 32)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

Genes affected

MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-11802721-A-G is Benign according to our data. Variant chr1-11802721-A-G is described in ClinVar as [Benign]. Clinvar id is 1237104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.236+160T>C		intron_variant		ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.236+160T>C		intron_variant		1	NM_005957.5	ENSP00000365775	A1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20735 AN: 152054 Hom.: 1512 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.136 AC: 20735 AN: 152172 Hom.: 1508 Cov.: 32 AF XY: 0.138 AC XY: 10256 AN XY: 74382

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.120

Alfa AF: 0.146 Hom.: 3852

Bravo AF: 0.130

Asia WGS AF: 0.152 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.069
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs17367504; hg19: chr1-11862778;