rs10486213

chr7-8203794-A-Gchr7-8203794-A-T

Variant summary

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

The NM_001136020.3(ICA1):c.579+14511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,262 control chromosomes in the GnomAD database, including 68,171 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 0.95 (68171 hom., cov: 31)
• Consequence: ICA1 NM_001136020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICA1	NM_001136020.3	c.579+14511T>C		intron_variant		ENST00000402384.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICA1	ENST00000402384.8	c.579+14511T>C		intron_variant		2	NM_001136020.3	A1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143896 AN: 152144 Hom.: 68108 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.946 AC: 144018 AN: 152262 Hom.: 68171 Cov.: 31 AF XY: 0.946 AC XY: 70454 AN XY: 74446

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.939

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.950

Alfa AF: 0.933 Hom.: 89464

Bravo AF: 0.948

Asia WGS AF: 0.940 AC: 3268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.14
Dann	Benign	0.54

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: rs10486213; hg19: chr7-8243424;