rs12356233

Positions:

• chr10-125846361-A-G

Variant summary

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

The NM_018180.3(DHX32):​c.1352-4427T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,058 control chromosomes in the GnomAD database, including 11,666 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 0.38 (11666 hom., cov: 33)
• Consequence: DHX32 NM_018180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

Genes affected

DHX32 (HGNC:16717): (DEAH-box helicase 32 (putative)) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Alternative splicing of this gene generates 2 transcript variants, but the full length nature of one of the variants has not been defined. [provided by RefSeq, Jul 2008]

BCCIP (HGNC:978): (BRCA2 and CDKN1A interacting protein) This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. This protein has also been implicated in the regulation of BRCA2 and RAD51 nuclear focus formation, double-strand break-induced homologous recombination, and cell cycle progression. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX32	NM_018180.3	c.1352-4427T>C		intron_variant		ENST00000284690.4	NP_060650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX32	ENST00000284690.4	c.1352-4427T>C		intron_variant		1	NM_018180.3	ENSP00000284690.3
DHX32	ENST00000368721.5	c.224-4427T>C		intron_variant		1		ENSP00000357710.1
BCCIP	ENST00000368759.5	c.850+5031A>G		intron_variant		1		ENSP00000357748.5

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58390 AN: 151940 Hom.: 11654 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.384 AC: 58433 AN: 152058 Hom.: 11666 Cov.: 33 AF XY: 0.381 AC XY: 28310 AN XY: 74306

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.390

Alfa AF: 0.429 Hom.: 7010

Bravo AF: 0.368

Asia WGS AF: 0.352 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.81

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: rs12356233; hg19: chr10-127534930;