chr1-210362934-C-A

Variant names:

• chr1-210362934-C-A
• rs11119469
• NM_018194.6:c.159+15C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018194.6(HHAT):​c.159+15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,566,260 control chromosomes in the GnomAD database, including 14,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1050 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13921 hom.)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.225
• Publications: 4 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, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000287354 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-210362934-C-A is Benign according to our data. Variant chr1-210362934-C-A is described in ClinVar as Benign. ClinVar VariationId is 1599919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018194.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	NM_018194.6	MANE Select	c.159+15C>A		intron	N/A	NP_060664.2	Q5VTY9-1
	HHAT	NM_001170587.3		c.162+15C>A		intron	N/A	NP_001164058.1	Q5VTY9-7
	HHAT	NM_001122834.4		c.159+15C>A		intron	N/A	NP_001116306.1	Q5VTY9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	ENST00000261458.8	TSL:2 MANE Select	c.159+15C>A		intron	N/A	ENSP00000261458.3	Q5VTY9-1
	HHAT	ENST00000426968.2	TSL:1	c.-31+15C>A		intron	N/A	ENSP00000413399.1	A0A075B6R5
	HHAT	ENST00000545154.5	TSL:2	c.162+15C>A		intron	N/A	ENSP00000438468.1	Q5VTY9-7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16141 AN: 151986 Hom.: 1047 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.112 AC: 28164 AN: 250442 AF XY: 0.117

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.0722

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.00131

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.135 AC: 190599 AN: 1414156 Hom.: 13921 Cov.: 24 AF XY: 0.135 AC XY: 95530 AN XY: 706380

African (AFR) AF: 0.0354 AC: 1156 AN: 32680

American (AMR) AF: 0.0748 AC: 3329 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 2529 AN: 25824

East Asian (EAS) AF: 0.000987 AC: 39 AN: 39510

South Asian (SAS) AF: 0.108 AC: 9172 AN: 85048

European-Finnish (FIN) AF: 0.138 AC: 7363 AN: 53388

Middle Eastern (MID) AF: 0.151 AC: 859 AN: 5692

European-Non Finnish (NFE) AF: 0.149 AC: 158829 AN: 1068592

Other (OTH) AF: 0.124 AC: 7323 AN: 58904

GnomAD4 genome AF: 0.106 AC: 16154 AN: 152104 Hom.: 1050 Cov.: 32 AF XY: 0.106 AC XY: 7880 AN XY: 74354

African (AFR) AF: 0.0389 AC: 1615 AN: 41486

American (AMR) AF: 0.0993 AC: 1518 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.109 AC: 527 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1468 AN: 10552

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10293 AN: 67994

Other (OTH) AF: 0.104 AC: 220 AN: 2108

Alfa AF: 0.121 Hom.: 303

Bravo AF: 0.0982

Asia WGS AF: 0.0650 AC: 228 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.74
PhyloP100		-0.23
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11119469; hg19: chr1-210536278;