rs7189489

Positions:

• chr16-86553056-A-C
• chr16-86553056-A-T

Variant summary

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

The ENST00000360900.11(MTHFSD):​c.124-910T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,968 control chromosomes in the GnomAD database, including 40,172 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 0.72 (40172 hom., cov: 31)
• Consequence: MTHFSD ENST00000360900.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFSD	NM_001159377.2	c.124-910T>G		intron_variant		ENST00000360900.11	NP_001152849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFSD	ENST00000360900.11	c.124-910T>G		intron_variant		1	NM_001159377.2	ENSP00000354152	A2

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108805 AN: 151850 Hom.: 40153 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.716 AC: 108865 AN: 151968 Hom.: 40172 Cov.: 31 AF XY: 0.718 AC XY: 53314 AN XY: 74302

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.734

Alfa AF: 0.775 Hom.: 9436

Bravo AF: 0.701

Asia WGS AF: 0.738 AC: 2566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.77

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: rs7189489; hg19: chr16-86586662;