rs4646410

Variant names:

• chr17-17505385-G-A
• rs4646410
• ENST00000671231.1:n.120+1261G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-17505385-G-A
• chr17-17505385-G-C

Variant summary

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

The ENST00000671231.1(ENSG00000286430):​n.120+1261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,866 control chromosomes in the GnomAD database, including 26,765 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 0.56 (26765 hom., cov: 31)
• Consequence: ENSG00000286430 ENST00000671231.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

Genes affected

ENSG00000286430 (HGNC:):

PEMT (HGNC:8830): (phosphatidylethanolamine N-methyltransferase) Phosphatidylcholine (PC) is the most abundant mammalian phospholipid. This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process. The protein isoforms encoded by this gene localize to the endoplasmic reticulum and mitochondria-associated membranes. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3	c.*406C>T		downstream_gene_variant		ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.*406C>T		downstream_gene_variant		1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85277 AN: 151748 Hom.: 26761 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.562 AC: 85309 AN: 151866 Hom.: 26765 Cov.: 31 AF XY: 0.557 AC XY: 41334 AN XY: 74216

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.570

Alfa AF: 0.679 Hom.: 31798

Bravo AF: 0.540

Asia WGS AF: 0.384 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646410; hg19: chr17-17408699;