rs629242

Positions:

• chr4-56276871-C-T

Variant summary

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

The NM_001393381.1(CRACD):​c.-17+4379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,136 control chromosomes in the GnomAD database, including 4,927 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 0.25 (4927 hom., cov: 32)
• Consequence: CRACD NM_001393381.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRACD	NM_001393381.1	c.-17+4379C>T		intron_variant		ENST00000682029.1	NP_001380310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRACD	ENST00000682029.1	c.-17+4379C>T		intron_variant			NM_001393381.1	ENSP00000507165	A2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38061 AN: 152018 Hom.: 4934 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.250 AC: 38064 AN: 152136 Hom.: 4927 Cov.: 32 AF XY: 0.248 AC XY: 18463 AN XY: 74354

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.266

Alfa AF: 0.227 Hom.: 8370

Bravo AF: 0.252

Asia WGS AF: 0.312 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs629242; hg19: chr4-57143037;