5-95750599-T-C

Variant names:

• chr5-95750599-T-C
• rs34897
• NM_014899.4:c.571-1640T>C

Variant summary

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

The NM_014899.4(RHOBTB3):​c.571-1640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,166 control chromosomes in the GnomAD database, including 13,001 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 0.40 (13001 hom., cov: 32)
• Consequence: RHOBTB3 NM_014899.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• Publications: 6 publications found

Genes affected

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOBTB3	NM_014899.4	c.571-1640T>C		intron_variant	Intron 4 of 11	ENST00000379982.8	NP_055714.3
RHOBTB3	XM_011543279.3	c.571-1640T>C		intron_variant	Intron 4 of 10		XP_011541581.1
RHOBTB3	XM_017009237.2	c.-12-1640T>C		intron_variant	Intron 4 of 11		XP_016864726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOBTB3	ENST00000379982.8	c.571-1640T>C		intron_variant	Intron 4 of 11	1	NM_014899.4	ENSP00000369318.3
RHOBTB3	ENST00000502541.1	n.291+2112T>C		intron_variant	Intron 2 of 3	5		ENSP00000421875.1
RHOBTB3	ENST00000504949.1	n.702-1640T>C		intron_variant	Intron 4 of 5	2
RHOBTB3	ENST00000510623.1	n.*66-1640T>C		intron_variant	Intron 2 of 2	2		ENSP00000423652.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61262 AN: 152048 Hom.: 12995 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.403 AC: 61293 AN: 152166 Hom.: 13001 Cov.: 32 AF XY: 0.407 AC XY: 30285 AN XY: 74372

African (AFR) AF: 0.307 AC: 12760 AN: 41520

American (AMR) AF: 0.371 AC: 5682 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3722 AN: 5180

South Asian (SAS) AF: 0.531 AC: 2561 AN: 4822

European-Finnish (FIN) AF: 0.455 AC: 4817 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28562 AN: 67984

Other (OTH) AF: 0.438 AC: 926 AN: 2112

Alfa AF: 0.408 Hom.: 2121

Bravo AF: 0.393

Asia WGS AF: 0.588 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.55
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs34897; hg19: chr5-95086303;