rs8074061

Positions:

• chr17-32274326-T-C

Variant summary

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

The NM_138328.3(RHBDL3):​c.135+6401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,022 control chromosomes in the GnomAD database, including 8,424 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 0.33 (8424 hom., cov: 32)
• Consequence: RHBDL3 NM_138328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

Genes affected

RHBDL3 (HGNC:16502): (rhomboid like 3) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be integral component of membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHBDL3	NM_138328.3	c.135+6401T>C		intron_variant		ENST00000269051.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHBDL3	ENST00000269051.9	c.135+6401T>C		intron_variant		1	NM_138328.3	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49442 AN: 151904 Hom.: 8413 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.325 AC: 49476 AN: 152022 Hom.: 8424 Cov.: 32 AF XY: 0.326 AC XY: 24188 AN XY: 74304

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.330

Alfa AF: 0.298 Hom.: 10975

Bravo AF: 0.321

Asia WGS AF: 0.270 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.37

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: rs8074061; hg19: chr17-30601345;