rs17143586

Variant names:

• chr7-8137767-C-A
• rs17143586
• NM_001136020.3:c.1060+1073G>T

Variant summary

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

The NM_001136020.3(ICA1):​c.1060+1073G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 152,248 control chromosomes in the GnomAD database, including 241 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 0.052 (241 hom., cov: 32)
• Consequence: ICA1 NM_001136020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 5 publications found

Genes affected

ICA1 (HGNC:5343): (islet cell autoantigen 1) This gene encodes a protein with an arfaptin homology domain that is found both in the cytosol and as membrane-bound form on the Golgi complex and immature secretory granules. This protein is believed to be an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICA1	NM_001136020.3	c.1060+1073G>T		intron_variant	Intron 12 of 13	ENST00000402384.8	NP_001129492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICA1	ENST00000402384.8	c.1060+1073G>T		intron_variant	Intron 12 of 13	2	NM_001136020.3	ENSP00000385570.3

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7897 AN: 152130 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0379

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

GnomAD4 genome AF: 0.0520 AC: 7920 AN: 152248 Hom.: 241 Cov.: 32 AF XY: 0.0525 AC XY: 3910 AN XY: 74436

African (AFR) AF: 0.0846 AC: 3516 AN: 41538

American (AMR) AF: 0.0377 AC: 577 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3466

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4822

European-Finnish (FIN) AF: 0.0568 AC: 602 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0423 AC: 2875 AN: 68004

Other (OTH) AF: 0.0389 AC: 82 AN: 2108

Alfa AF: 0.0506 Hom.: 191

Bravo AF: 0.0506

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.82
DANN	Benign	0.75
PhyloP100		-0.60
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: rs17143586; hg19: chr7-8177397;