chr1-38914713-T-C

Variant names:

• chr1-38914713-T-C
• rs4246511
• NM_017821.5:c.395+849A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017821.5(RHBDL2):​c.395+849A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,660 control chromosomes in the GnomAD database, including 25,259 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 0.55 (25259 hom., cov: 29)
• Consequence: RHBDL2 NM_017821.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 32 publications found

Genes affected

RHBDL2 (HGNC:16083): (rhomboid like 2) The protein encoded by this gene is a member of the rhomboid family of integral membrane proteins. This family contains proteins that are related to Drosophila rhomboid protein. Members of this family are found in both prokaryotes and eukaryotes and are thought to function as intramembrane serine proteases. The encoded protein is thought to release soluble growth factors by proteolytic cleavage of certain membrane-bound substrates, including ephrin B2 and ephrin B3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

RRAGC-DT (HGNC:55793): (RRAGC divergent transcript)

LOC105378662 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDL2	NM_017821.5	c.395+849A>G		intron_variant	Intron 3 of 7	ENST00000372990.6	NP_060291.2
RHBDL2	NM_001304746.2	c.635+849A>G		intron_variant	Intron 3 of 7		NP_001291675.1
LOC105378662	XR_001737994.2	n.89+1085T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBDL2	ENST00000372990.6	c.395+849A>G		intron_variant	Intron 3 of 7	5	NM_017821.5	ENSP00000362081.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83484 AN: 151540 Hom.: 25258 Cov.: 29

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.551 AC: 83511 AN: 151660 Hom.: 25259 Cov.: 29 AF XY: 0.546 AC XY: 40493 AN XY: 74104

African (AFR) AF: 0.303 AC: 12510 AN: 41346

American (AMR) AF: 0.600 AC: 9122 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2058 AN: 3464

East Asian (EAS) AF: 0.404 AC: 2062 AN: 5108

South Asian (SAS) AF: 0.417 AC: 2001 AN: 4802

European-Finnish (FIN) AF: 0.648 AC: 6812 AN: 10518

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46862 AN: 67906

Other (OTH) AF: 0.571 AC: 1202 AN: 2104

Alfa AF: 0.634 Hom.: 63374

Bravo AF: 0.543

Asia WGS AF: 0.400 AC: 1391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.76
PhyloP100		-0.89
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: rs4246511; hg19: chr1-39380385; COSMIC: COSV56710134; COSMIC: COSV56710134;