rs17143586

chr7-8137767-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ICA1	NM_001136020.3	c.1060+1073G>T		intron_variant		ENST00000402384.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICA1	ENST00000402384.8	c.1060+1073G>T		intron_variant		2	NM_001136020.3	A1

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

Gnomad4 AFR AF: 0.0846

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0477 Hom.: 71

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

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: rs17143586; hg19: chr7-8177397;