7-8203794-A-G

Variant names:

• chr7-8203794-A-G
• rs10486213
• NM_001136020.3:c.579+14511T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICA1	NM_001136020.3	MANE Select	c.579+14511T>C		intron	N/A	NP_001129492.1
	ICA1	NM_001350826.2		c.579+14511T>C		intron	N/A	NP_001337755.1
	ICA1	NM_001350827.2		c.579+14511T>C		intron	N/A	NP_001337756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICA1	ENST00000402384.8	TSL:2 MANE Select	c.579+14511T>C		intron	N/A	ENSP00000385570.3
	ICA1	ENST00000422063.6	TSL:1	c.579+14511T>C		intron	N/A	ENSP00000403982.2
	ICA1	ENST00000396675.7	TSL:1	c.579+14511T>C		intron	N/A	ENSP00000379908.3

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

African (AFR) AF: 0.984 AC: 40886 AN: 41540

American (AMR) AF: 0.932 AC: 14257 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3118 AN: 3470

East Asian (EAS) AF: 0.927 AC: 4805 AN: 5184

South Asian (SAS) AF: 0.939 AC: 4522 AN: 4818

European-Finnish (FIN) AF: 0.954 AC: 10122 AN: 10608

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63183 AN: 68024

Other (OTH) AF: 0.950 AC: 2010 AN: 2116

Alfa AF: 0.935 Hom.: 113432

Bravo AF: 0.948

Asia WGS AF: 0.940 AC: 3268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.54
PhyloP100		-2.7
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: rs10486213; hg19: chr7-8243424;