rs8074061

Variant names:

• chr17-32274326-T-C
• rs8074061
• NM_138328.3:c.135+6401T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RHBDL3	NM_138328.3	c.135+6401T>C		intron_variant	Intron 2 of 8	ENST00000269051.9	NP_612201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBDL3	ENST00000269051.9	c.135+6401T>C		intron_variant	Intron 2 of 8	1	NM_138328.3	ENSP00000269051.4

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

African (AFR) AF: 0.427 AC: 17696 AN: 41450

American (AMR) AF: 0.258 AC: 3935 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3470

East Asian (EAS) AF: 0.145 AC: 749 AN: 5182

South Asian (SAS) AF: 0.393 AC: 1891 AN: 4814

European-Finnish (FIN) AF: 0.336 AC: 3547 AN: 10564

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19547 AN: 67962

Other (OTH) AF: 0.330 AC: 697 AN: 2110

Alfa AF: 0.297 Hom.: 26420

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
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8074061; hg19: chr17-30601345;