rs4951508

chr1-210656133-T-C

Variant summary

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

The NM_018194.6(HHAT):c.1391-18155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,140 control chromosomes in the GnomAD database, including 34,182 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 0.65 (34182 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HHAT	NM_018194.6	c.1391-18155T>C		intron_variant		ENST00000261458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HHAT	ENST00000261458.8	c.1391-18155T>C		intron_variant		2	NM_018194.6	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98642 AN: 152022 Hom.: 34172 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.649 AC: 98694 AN: 152140 Hom.: 34182 Cov.: 32 AF XY: 0.649 AC XY: 48241 AN XY: 74386

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.683

Alfa AF: 0.752 Hom.: 58341

Bravo AF: 0.632

Asia WGS AF: 0.587 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.2
Dann	Benign	0.29

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: rs4951508; hg19: chr1-210829477; COSMIC: COSV54795012;