rs2192346

Variant names:

• chr7-8136671-G-A
• rs2192346
• NM_001136020.3:c.1060+2169C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-8136671-G-A
• chr7-8136671-G-T

Variant summary

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

The NM_001136020.3(ICA1):​c.1060+2169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,100 control chromosomes in the GnomAD database, including 43,637 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 0.76 (43637 hom., cov: 32)
• Consequence: ICA1 NM_001136020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICA1	NM_001136020.3	c.1060+2169C>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+2169C>T		intron_variant	Intron 12 of 13	2	NM_001136020.3	ENSP00000385570.3

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114934 AN: 151982 Hom.: 43615 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.756 AC: 114994 AN: 152100 Hom.: 43637 Cov.: 32 AF XY: 0.762 AC XY: 56635 AN XY: 74350

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.775

Alfa AF: 0.746 Hom.: 17603

Bravo AF: 0.759

Asia WGS AF: 0.834 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2192346; hg19: chr7-8176301;