rs9915078

Positions:

• chr17-35116196-A-G

Variant summary

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

The NM_002878.4(RAD51D):​c.263+2305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,080 control chromosomes in the GnomAD database, including 2,574 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 0.16 (2574 hom., cov: 32)
• Consequence: RAD51D NM_002878.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

Genes affected

RAD51D (HGNC:9823): (RAD51 paralog D) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, which are known to be involved in the homologous recombination and repair of DNA. This protein forms a complex with several other members of the RAD51 family, including RAD51L1, RAD51L2, and XRCC2. The protein complex formed with this protein has been shown to catalyze homologous pairing between single- and double-stranded DNA, and is thought to play a role in the early stage of recombinational repair of DNA. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream ring finger and FYVE-like domain containing 1 (RFFL) gene. [provided by RefSeq, Jan 2011]

RAD51L3-RFFL (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51D	NM_002878.4	c.263+2305T>C		intron_variant		ENST00000345365.11	NP_002869.3
RAD51L3-RFFL	NR_037714.1	n.232+5095T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51D	ENST00000345365.11	c.263+2305T>C		intron_variant		1	NM_002878.4	ENSP00000338790	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23616 AN: 151962 Hom.: 2570 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.155 AC: 23647 AN: 152080 Hom.: 2574 Cov.: 32 AF XY: 0.156 AC XY: 11620 AN XY: 74360

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.136

Alfa AF: 0.131 Hom.: 473

Bravo AF: 0.162

Asia WGS AF: 0.146 AC: 510 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	0.63
DANN	Benign	0.63

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: rs9915078; hg19: chr17-33443215;