rs2233837

Positions:

• chr20-31484597-G-A

Variant summary

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

The NM_014012.6(REM1):​c.*167G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 882,908 control chromosomes in the GnomAD database, including 85 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 0.017 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (23 hom.)
• Consequence: REM1 NM_014012.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

Genes affected

REM1 (HGNC:15922): (RRAD and GEM like GTPase 1) The protein encoded by this gene is a GTPase and member of the RAS-like GTP-binding protein family. The encoded protein is expressed in endothelial cells, where it promotes reorganization of the actin cytoskeleton and morphological changes in the cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REM1	NM_014012.6	c.*167G>A		3_prime_UTR_variant	5/5	ENST00000201979.3	NP_054731.2
REM1	XM_005260404.1	c.*167G>A		3_prime_UTR_variant	5/5		XP_005260461.1
REM1	XM_017027833.2	c.*167G>A		3_prime_UTR_variant	5/5		XP_016883322.1
REM1	XM_011528795.1	c.*167G>A		3_prime_UTR_variant	5/5		XP_011527097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REM1	ENST00000201979.3	c.*167G>A		3_prime_UTR_variant	5/5	1	NM_014012.6	ENSP00000201979.2

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2580 AN: 152240 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00693

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00162 AC: 1187 AN: 730550 Hom.: 23 Cov.: 10 AF XY: 0.00142 AC XY: 517 AN XY: 363648

Gnomad4 AFR exome AF: 0.0615

Gnomad4 AMR exome AF: 0.00522

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000225

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.00474

GnomAD4 genome AF: 0.0170 AC: 2589 AN: 152358 Hom.: 62 Cov.: 33 AF XY: 0.0165 AC XY: 1227 AN XY: 74514

Gnomad4 AFR AF: 0.0584

Gnomad4 AMR AF: 0.00692

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00874 Hom.: 3

Bravo AF: 0.0198

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.74
DANN	Benign	0.47

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: rs2233837; hg19: chr20-30072400;