rs6659502

Positions:

• chr1-210672986-G-A
• chr1-210672986-G-C
• chr1-210672986-G-T

Variant summary

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

The NM_018194.6(HHAT):​c.1391-1302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,142 control chromosomes in the GnomAD database, including 42,779 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 0.73 (42779 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

Genes affected

HHAT (HGNC:18270): (hedgehog acyltransferase) 'Skinny hedgehog' (SKI1) encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of 'hedgehog' (see MIM 600725).[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHAT	NM_018194.6	c.1391-1302G>A		intron_variant		ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.1391-1302G>A		intron_variant		2	NM_018194.6	ENSP00000261458	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110495 AN: 152022 Hom.: 42775 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.821

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.726 AC: 110527 AN: 152142 Hom.: 42779 Cov.: 32 AF XY: 0.728 AC XY: 54154 AN XY: 74386

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.766

Alfa AF: 0.798 Hom.: 21231

Bravo AF: 0.701

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6659502; hg19: chr1-210846327;