rs11646114

Variant names:

• chr16-86550168-T-A
• rs11646114
• NM_001159377.2:c.238-1591A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTHFSD	NM_001159377.2	c.238-1591A>T		intron_variant	Intron 3 of 7	ENST00000360900.11	NP_001152849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFSD	ENST00000360900.11	c.238-1591A>T		intron_variant	Intron 3 of 7	1	NM_001159377.2	ENSP00000354152.6

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

African (AFR) AF: 0.00962 AC: 400 AN: 41580

American (AMR) AF: 0.0442 AC: 677 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 281 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4830

European-Finnish (FIN) AF: 0.0898 AC: 953 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3840 AN: 68030

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

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
PhyloP100		1.0
Mutation Taster		=100/0	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: rs11646114; hg19: chr16-86583774;