rs4665947

Positions:

• chr2-27125161-T-C

Variant summary

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

The NM_032604.4(ABHD1):​c.114+1099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,392 control chromosomes in the GnomAD database, including 9,171 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 0.34 (9167 hom., cov: 31)
  • Exomes 𝑓: 0.41 (4 hom.)
• Consequence: ABHD1 NM_032604.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

Genes affected

ABHD1 (HGNC:17553): (abhydrolase domain containing 1) This gene is a member of the AB hydrolase superfamily and encodes a protein with an alpha/beta hydrolase fold. This domain is common to a number of hydrolytic enzymes of widely differing phylogenetic origins and catalytic functions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD1	NM_032604.4	c.114+1099T>C		intron_variant		ENST00000316470.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD1	ENST00000316470.9	c.114+1099T>C		intron_variant		1	NM_032604.4	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50813 AN: 151260 Hom.: 9140 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.412 AC: 14 AN: 34 Hom.: 4 Cov.: 0 AF XY: 0.318 AC XY: 7 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.336 AC: 50865 AN: 151358 Hom.: 9167 Cov.: 31 AF XY: 0.337 AC XY: 24871 AN XY: 73900

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.377

Alfa AF: 0.370 Hom.: 14331

Bravo AF: 0.355

Asia WGS AF: 0.333 AC: 1145 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.64

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: rs4665947; hg19: chr2-27348029;