rs6463768

Variant names:

• chr7-8118257-C-G
• rs6463768
• NM_001136020.3:c.1331-4213G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-8118257-C-G
• chr7-8118257-C-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.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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.1331-4213G>C		intron	N/A	NP_001129492.1	A0A024RA29
	ICA1	NM_001350826.2		c.1418-4213G>C		intron	N/A	NP_001337755.1	Q05084-2
	ICA1	NM_001350827.2		c.1418-4213G>C		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.1331-4213G>C		intron	N/A	ENSP00000385570.3	Q05084-1
	ICA1	ENST00000422063.6	TSL:1	c.1418-4213G>C		intron	N/A	ENSP00000403982.2	Q05084-2
	ICA1	ENST00000396675.7	TSL:1	c.1331-4213G>C		intron	N/A	ENSP00000379908.3	Q05084-1

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

African (AFR) AF: 0.887 AC: 36854 AN: 41526

American (AMR) AF: 0.909 AC: 13908 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3345 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4529 AN: 5190

South Asian (SAS) AF: 0.904 AC: 4352 AN: 4816

European-Finnish (FIN) AF: 0.941 AC: 9977 AN: 10604

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65112 AN: 68032

Other (OTH) AF: 0.937 AC: 1983 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.22
PhyloP100		-1.1
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: rs6463768; hg19: chr7-8157887;