rs7527939

Positions:

• chr1-210362681-C-T

Variant summary

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

The NM_018194.6(HHAT):​c.92-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,076 control chromosomes in the GnomAD database, including 9,200 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 0.29 (9200 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHAT	NM_018194.6	c.92-171C>T		intron_variant		ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.92-171C>T		intron_variant		2	NM_018194.6	ENSP00000261458	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44813 AN: 151958 Hom.: 9196 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.295 AC: 44852 AN: 152076 Hom.: 9200 Cov.: 32 AF XY: 0.293 AC XY: 21781 AN XY: 74338

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.249

Alfa AF: 0.197 Hom.: 4891

Bravo AF: 0.307

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.74

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: rs7527939; hg19: chr1-210536025; COSMIC: COSV54801731; COSMIC: COSV54801731;