chr1-210656133-T-C

Variant names:

• chr1-210656133-T-C
• rs4951508
• NM_018194.6:c.1391-18155T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261458.8(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 ENST00000261458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• Publications: 6 publications found

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]

HHAT Gene-Disease associations (from GenCC):

• chondrodysplasia-pseudohermaphroditism syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261458.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	NM_018194.6	MANE Select	c.1391-18155T>C		intron	N/A	NP_060664.2
	HHAT	NM_001170587.3		c.1394-18155T>C		intron	N/A	NP_001164058.1
	HHAT	NM_001122834.4		c.1391-18155T>C		intron	N/A	NP_001116306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	ENST00000261458.8	TSL:2 MANE Select	c.1391-18155T>C		intron	N/A	ENSP00000261458.3
	HHAT	ENST00000545154.5	TSL:2	c.1394-18155T>C		intron	N/A	ENSP00000438468.1
	HHAT	ENST00000367010.5	TSL:2	c.1391-18155T>C		intron	N/A	ENSP00000355977.1

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

African (AFR) AF: 0.393 AC: 16312 AN: 41490

American (AMR) AF: 0.693 AC: 10592 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2754 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2613 AN: 5160

South Asian (SAS) AF: 0.650 AC: 3132 AN: 4818

European-Finnish (FIN) AF: 0.747 AC: 7923 AN: 10602

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53135 AN: 67988

Other (OTH) AF: 0.683 AC: 1443 AN: 2112

Alfa AF: 0.741 Hom.: 71730

Bravo AF: 0.632

Asia WGS AF: 0.587 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.29
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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