rs12978500

Variant names:

• chr19-406934-C-A
• rs12978500
• NM_001136263.2:c.*162G>T

Variant summary

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

The NM_001136263.2(C2CD4C):​c.*162G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 546,802 control chromosomes in the GnomAD database, including 131,840 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 0.68 (35267 hom., cov: 32)
  • Exomes 𝑓: 0.69 (96573 hom.)
• Consequence: C2CD4C NM_001136263.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 8 publications found

Genes affected

C2CD4C (HGNC:29417): (C2 calcium dependent domain containing 4C) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD4C	NM_001136263.2	c.*162G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000332235.8	NP_001129735.1
C2CD4C	XM_011527694.2	c.1179+249G>T		intron_variant	Intron 2 of 2		XP_011525996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD4C	ENST00000332235.8	c.*162G>T		3_prime_UTR_variant	Exon 2 of 2	2	NM_001136263.2	ENSP00000328677.4

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102743 AN: 151628 Hom.: 35253 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.692 AC: 273464 AN: 395056 Hom.: 96573 Cov.: 5 AF XY: 0.694 AC XY: 143076 AN XY: 206212

African (AFR) AF: 0.553 AC: 5469 AN: 9898

American (AMR) AF: 0.739 AC: 10214 AN: 13830

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 6998 AN: 11332

East Asian (EAS) AF: 0.816 AC: 18963 AN: 23242

South Asian (SAS) AF: 0.715 AC: 27588 AN: 38594

European-Finnish (FIN) AF: 0.638 AC: 15126 AN: 23724

Middle Eastern (MID) AF: 0.654 AC: 1128 AN: 1726

European-Non Finnish (NFE) AF: 0.690 AC: 172934 AN: 250522

Other (OTH) AF: 0.678 AC: 15044 AN: 22188

GnomAD4 genome AF: 0.677 AC: 102804 AN: 151746 Hom.: 35267 Cov.: 32 AF XY: 0.678 AC XY: 50311 AN XY: 74192

African (AFR) AF: 0.578 AC: 23879 AN: 41328

American (AMR) AF: 0.736 AC: 11246 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2214 AN: 3466

East Asian (EAS) AF: 0.814 AC: 4161 AN: 5110

South Asian (SAS) AF: 0.745 AC: 3591 AN: 4818

European-Finnish (FIN) AF: 0.665 AC: 6995 AN: 10522

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48342 AN: 67912

Other (OTH) AF: 0.694 AC: 1465 AN: 2112

Alfa AF: 0.699 Hom.: 105308

Bravo AF: 0.678

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.68
PhyloP100		0.12
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: rs12978500; hg19: chr19-406934; COSMIC: COSV59967661;