rs12116836

Positions:

• chr1-210658476-A-G

Variant summary

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

The NM_018194.6(HHAT):​c.1391-15812A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,114 control chromosomes in the GnomAD database, including 5,998 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 0.26 (5998 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HHAT	NM_018194.6	c.1391-15812A>G		intron_variant		ENST00000261458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HHAT	ENST00000261458.8	c.1391-15812A>G		intron_variant		2	NM_018194.6	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38985 AN: 151996 Hom.: 6001 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.256 AC: 38990 AN: 152114 Hom.: 5998 Cov.: 32 AF XY: 0.257 AC XY: 19084 AN XY: 74356

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.278

Alfa AF: 0.318 Hom.: 7807

Bravo AF: 0.244

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.063
DANN	Benign	0.85

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: rs12116836; hg19: chr1-210831820;