rs11646114

chr16-86550168-T-A

Variant summary

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

The NM_001159377.2(MTHFSD):c.238-1591A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,318 control chromosomes in the GnomAD database, including 218 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 0.042 (218 hom., cov: 34)
• Consequence: MTHFSD NM_001159377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

MTHFSD (HGNC:25778): (methenyltetrahydrofolate synthetase domain containing) Enables RNA binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFSD	NM_001159377.2	c.238-1591A>T		intron_variant		ENST00000360900.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFSD	ENST00000360900.11	c.238-1591A>T		intron_variant		1	NM_001159377.2	A2

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6421 AN: 152200 Hom.: 218 Cov.: 34

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0811

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0421 AC: 6414 AN: 152318 Hom.: 218 Cov.: 34 AF XY: 0.0430 AC XY: 3204 AN XY: 74476

Gnomad4 AFR AF: 0.00962

Gnomad4 AMR AF: 0.0442

Gnomad4 ASJ AF: 0.0811

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0898

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0497 Hom.: 25

Bravo AF: 0.0375

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.2
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs11646114; hg19: chr16-86583774;