rs6463768

chr7-8118257-C-Gchr7-8118257-C-T

Variant summary

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

The NM_001136020.3(ICA1):c.1331-4213G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,254 control chromosomes in the GnomAD database, including 65,537 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 0.93 (65537 hom., cov: 33)
• Consequence: ICA1 NM_001136020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICA1	NM_001136020.3	c.1331-4213G>C		intron_variant		ENST00000402384.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICA1	ENST00000402384.8	c.1331-4213G>C		intron_variant		2	NM_001136020.3	A1

Frequencies

GnomAD3 genomes AF: 0.927 AC: 141082 AN: 152136 Hom.: 65502 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.927 AC: 141174 AN: 152254 Hom.: 65537 Cov.: 33 AF XY: 0.925 AC XY: 68866 AN XY: 74426

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.964

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.957

Gnomad4 OTH AF: 0.937

Alfa AF: 0.944 Hom.: 8428

Bravo AF: 0.923

Asia WGS AF: 0.871 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.30
Dann	Benign	0.22

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: rs6463768; hg19: chr7-8157887;