2-9474570-G-C

Variant names:

• chr2-9474570-G-C
• rs572817126
• NM_001039613.3:c.4G>C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001039613.3(IAH1):​c.4G>C​(p.Ala2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,485,764 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00035 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: IAH1 NM_001039613.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

Genes affected

IAH1 (HGNC:27696): (isoamyl acetate hydrolyzing esterase 1 (putative)) Enables identical protein binding activity. Predicted to be involved in lipid catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29471958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IAH1	NM_001039613.3	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 6	ENST00000497473.6	NP_001034702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IAH1	ENST00000497473.6	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 6	1	NM_001039613.3	ENSP00000417580.1

Frequencies

GnomAD3 genomes AF: 0.000352 AC: 53 AN: 150550 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000399

Gnomad OTH AF: 0.000964

GnomAD3 exomes AF: 0.000314 AC: 47 AN: 149588 Hom.: 0 AF XY: 0.000188 AC XY: 16 AN XY: 85330

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000175

Gnomad OTH exome AF: 0.00143

GnomAD4 exome AF: 0.000246 AC: 329 AN: 1335112 Hom.: 1 Cov.: 31 AF XY: 0.000247 AC XY: 164 AN XY: 663660

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000242

Gnomad4 OTH exome AF: 0.000275

GnomAD4 genome AF: 0.000352 AC: 53 AN: 150652 Hom.: 1 Cov.: 33 AF XY: 0.000299 AC XY: 22 AN XY: 73648

Gnomad4 AFR AF: 0.0000740

Gnomad4 AMR AF: 0.00138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000399

Gnomad4 OTH AF: 0.000954

Bravo AF: 0.000431

ExAC AF: 0.000172 AC: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.039	D
Polyphen		0.70	P
Vest4		0.60
MutPred		0.24		Gain of loop (P = 0.0435);
MVP		0.57
MPC		0.60
ClinPred		0.068	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.74

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: rs572817126; hg19: chr2-9614699;