12-22494922-G-T

Position:

• chr12-22494922-G-T

Variant summary

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

The NM_001286176.2(C2CD5):​c.1148-1585C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,720 control chromosomes in the GnomAD database, including 31,966 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 0.60 (31966 hom., cov: 31)
• Consequence: C2CD5 NM_001286176.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

Genes affected

C2CD5 (HGNC:29062): (C2 calcium dependent domain containing 5) Enables calcium ion binding activity and calcium-dependent phospholipid binding activity. Involved in cellular response to insulin stimulus; intracellular protein transmembrane transport; and positive regulation of transport. Located in several cellular components, including centriolar satellite; cytoplasmic vesicle membrane; and ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2CD5-AS1 (HGNC:55961): (C2CD5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD5	NM_001286176.2	c.1148-1585C>A		intron_variant		ENST00000446597.6	NP_001273105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD5	ENST00000446597.6	c.1148-1585C>A		intron_variant		1	NM_001286176.2	ENSP00000388756	P4
C2CD5-AS1	ENST00000661495.1	n.171+85515G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91156 AN: 151602 Hom.: 31958 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.601 AC: 91176 AN: 151720 Hom.: 31966 Cov.: 31 AF XY: 0.595 AC XY: 44117 AN XY: 74152

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.644

Alfa AF: 0.756 Hom.: 54794

Bravo AF: 0.577

Asia WGS AF: 0.330 AC: 1139 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10505879; hg19: chr12-22647856;