chr1-210480030-T-C

Position:

• chr1-210480030-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.1007+15375T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,086 control chromosomes in the GnomAD database, including 30,258 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 0.62 (30258 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHAT	NM_018194.6	c.1007+15375T>C		intron_variant		ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.1007+15375T>C		intron_variant		2	NM_018194.6	ENSP00000261458	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93903 AN: 151968 Hom.: 30217 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.618 AC: 94007 AN: 152086 Hom.: 30258 Cov.: 32 AF XY: 0.616 AC XY: 45819 AN XY: 74332

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.596

Alfa AF: 0.537 Hom.: 29342

Bravo AF: 0.638

Asia WGS AF: 0.648 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.61

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: rs2050187; hg19: chr1-210653374;