17-32287685-A-T

Variant names:

• chr17-32287685-A-T
• rs753750
• NM_138328.3:c.295-1107A>T

Variant summary

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

The NM_138328.3(RHBDL3):​c.295-1107A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,062 control chromosomes in the GnomAD database, including 8,977 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 (8977 hom., cov: 32)
• Consequence: RHBDL3 NM_138328.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDL3	NM_138328.3	c.295-1107A>T		intron_variant	Intron 3 of 8	ENST00000269051.9	NP_612201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBDL3	ENST00000269051.9	c.295-1107A>T		intron_variant	Intron 3 of 8	1	NM_138328.3	ENSP00000269051.4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50166 AN: 151944 Hom.: 8953 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.330 AC: 50227 AN: 152062 Hom.: 8977 Cov.: 32 AF XY: 0.326 AC XY: 24256 AN XY: 74338

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.0648

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.325

Alfa AF: 0.113 Hom.: 184

Bravo AF: 0.332

Asia WGS AF: 0.175 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
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: rs753750; hg19: chr17-30614704;