rs6834736

Positions:

• chr4-56328359-C-G

Variant summary

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

The NM_001393381.1(CRACD):​c.*555C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 517,996 control chromosomes in the GnomAD database, including 81,629 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 0.56 (23978 hom., cov: 32)
  • Exomes 𝑓: 0.56 (57651 hom.)
• Consequence: CRACD NM_001393381.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972

Genes affected

CRACD (HGNC:29219): (capping protein inhibiting regulator of actin dynamics) Involved in negative regulation of barbed-end actin filament capping. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRACD	NM_001393381.1	c.*555C>G		3_prime_UTR_variant	11/11	ENST00000682029.1	NP_001380310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRACD	ENST00000682029.1	c.*555C>G		3_prime_UTR_variant	11/11		NM_001393381.1	ENSP00000507165.1
CRACD	ENST00000264229.11	c.*555C>G		3_prime_UTR_variant	11/11	2		ENSP00000264229.6
CRACD	ENST00000504228.6	c.*555C>G		3_prime_UTR_variant	10/10	5		ENSP00000423366.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84785 AN: 151830 Hom.: 23965 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.557

GnomAD3 exomes AF: 0.550 AC: 127160 AN: 231234 Hom.: 36102 AF XY: 0.546 AC XY: 69710 AN XY: 127572

Gnomad AFR exome AF: 0.587

Gnomad AMR exome AF: 0.683

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.266

Gnomad SAS exome AF: 0.576

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.549

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.556 AC: 203419 AN: 366048 Hom.: 57651 Cov.: 0 AF XY: 0.554 AC XY: 116232 AN XY: 209902

Gnomad4 AFR exome AF: 0.584

Gnomad4 AMR exome AF: 0.681

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.578

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.558 AC: 84846 AN: 151948 Hom.: 23978 Cov.: 32 AF XY: 0.557 AC XY: 41389 AN XY: 74276

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.551

Alfa AF: 0.544 Hom.: 4151

Bravo AF: 0.566

Asia WGS AF: 0.442 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6834736; hg19: chr4-57194525; COSMIC: COSV51722842; COSMIC: COSV51722842;