7-8167985-G-A

Variant names:

• chr7-8167985-G-A
• rs11764012
• NM_001136020.3:c.580-9333C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136020.3(ICA1):​c.580-9333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,840 control chromosomes in the GnomAD database, including 19,210 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 0.45 (19210 hom., cov: 31)
• Consequence: ICA1 NM_001136020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• Publications: 6 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]

ENSG00000304515 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICA1	NM_001136020.3	MANE Select	c.580-9333C>T		intron	N/A	NP_001129492.1	A0A024RA29
	ICA1	NM_001350826.2		c.580-9333C>T		intron	N/A	NP_001337755.1	Q05084-2
	ICA1	NM_001350827.2		c.580-9333C>T		intron	N/A	NP_001337756.1	Q05084-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICA1	ENST00000402384.8	TSL:2 MANE Select	c.580-9333C>T		intron	N/A	ENSP00000385570.3	Q05084-1
	ICA1	ENST00000422063.6	TSL:1	c.580-9333C>T		intron	N/A	ENSP00000403982.2	Q05084-2
	ICA1	ENST00000396675.7	TSL:1	c.580-9333C>T		intron	N/A	ENSP00000379908.3	Q05084-1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68273 AN: 151720 Hom.: 19177 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.450 AC: 68355 AN: 151840 Hom.: 19210 Cov.: 31 AF XY: 0.447 AC XY: 33166 AN XY: 74212

African (AFR) AF: 0.807 AC: 33434 AN: 41434

American (AMR) AF: 0.295 AC: 4487 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3464

East Asian (EAS) AF: 0.188 AC: 971 AN: 5160

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4019 AN: 10542

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21422 AN: 67884

Other (OTH) AF: 0.413 AC: 870 AN: 2106

Alfa AF: 0.394 Hom.: 15998

Bravo AF: 0.458

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.39
PhyloP100		0.70
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: rs11764012; hg19: chr7-8207615;