1-11790505-CA-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_005957(MTHFR):c.*174del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 152222 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Consequence

MTHFR
NM_005957 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.27

Links

MTHFR (HGNC:7436):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected. gnomad allele frequency = 0.00114 (174/152222) while in subpopulation NFE AF= 0.00228 (155/68034). AF 95% confidence interval is 0.00198. There are 0 homozygotes in gnomad. There are 81 alleles in male gnomad subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5 linkuse as main transcript	c.*174del		3_prime_UTR_variant	12/12	ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9 linkuse as main transcript	c.*174del		3_prime_UTR_variant	12/12	1	NM_005957.5	A1	P42898-1

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

174

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00186

AC:

2385

AN:

1279974

Hom.:

AF XY:

0.00181

AC XY:

1130

AN XY:

623090

show subpopulations

Gnomad4 AFR exome

AF:

0.000142

Gnomad4 AMR exome

AF:

0.000423

Gnomad4 ASJ exome

AF:

0.0000525

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000257

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00126

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00114

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neural tube defects, folate-sensitive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over