rs7189489

Variant names:

• chr16-86553056-A-C
• rs7189489
• NM_001159377.2:c.124-910T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-86553056-A-C
• chr16-86553056-A-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.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 NM_001159377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159377.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFSD	NM_001159377.2	MANE Select	c.124-910T>G		intron	N/A	NP_001152849.1	Q2M296-1
	MTHFSD	NM_001159378.2		c.124-764T>G		intron	N/A	NP_001152850.1	Q2M296-3
	MTHFSD	NM_001159379.2		c.121-764T>G		intron	N/A	NP_001152851.1	Q2M296-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFSD	ENST00000360900.11	TSL:1 MANE Select	c.124-910T>G		intron	N/A	ENSP00000354152.6	Q2M296-1
	MTHFSD	ENST00000381214.9	TSL:1	c.124-764T>G		intron	N/A	ENSP00000370612.5	Q2M296-3
	MTHFSD	ENST00000543303.6	TSL:1	c.121-764T>G		intron	N/A	ENSP00000444003.2	Q2M296-4

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

African (AFR) AF: 0.519 AC: 21477 AN: 41374

American (AMR) AF: 0.769 AC: 11736 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2605 AN: 3470

East Asian (EAS) AF: 0.681 AC: 3519 AN: 5164

South Asian (SAS) AF: 0.736 AC: 3543 AN: 4812

European-Finnish (FIN) AF: 0.829 AC: 8765 AN: 10572

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.806 AC: 54770 AN: 67986

Other (OTH) AF: 0.734 AC: 1554 AN: 2116

Alfa AF: 0.770 Hom.: 9545

Bravo AF: 0.701

Asia WGS AF: 0.738 AC: 2566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.77
PhyloP100		0.81
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: rs7189489; hg19: chr16-86586662;