rs4725072

Positions:

• chr7-8134957-A-C
• chr7-8134957-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.1060+3883T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,222 control chromosomes in the GnomAD database, including 70,026 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 0.96 (70026 hom., cov: 30)
• Consequence: ICA1 NM_001136020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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 = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICA1	NM_001136020.3	c.1060+3883T>G		intron_variant		ENST00000402384.8	NP_001129492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICA1	ENST00000402384.8	c.1060+3883T>G		intron_variant		2	NM_001136020.3	ENSP00000385570	A1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145864 AN: 152104 Hom.: 69967 Cov.: 30

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.959 AC: 145982 AN: 152222 Hom.: 70026 Cov.: 30 AF XY: 0.961 AC XY: 71504 AN XY: 74418

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.957

Alfa AF: 0.949 Hom.: 17147

Bravo AF: 0.961

Asia WGS AF: 0.986 AC: 3429 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	3.4
DANN	Benign	0.79

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: rs4725072; hg19: chr7-8174587;