rs1056189

Positions:

• chr5-149634855-A-G
• chr5-149634855-A-T

Variant summary

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

The NM_001001669.3(ARHGEF37):​c.*2664A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,532 control chromosomes in the GnomAD database, including 1,452 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 0.11 (1452 hom., cov: 32)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: ARHGEF37 NM_001001669.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

Genes affected

ARHGEF37 (HGNC:34430): (Rho guanine nucleotide exchange factor 37) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF37	NM_001001669.3	c.*2664A>G		3_prime_UTR_variant	13/13	ENST00000333677.7	NP_001001669.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF37	ENST00000333677.7	c.*2664A>G		3_prime_UTR_variant	13/13	2	NM_001001669.3	ENSP00000328083.6

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16859 AN: 152066 Hom.: 1444 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0144 AC: 5 AN: 348 Hom.: 0 Cov.: 0 AF XY: 0.00962 AC XY: 2 AN XY: 208

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.111 AC: 16903 AN: 152184 Hom.: 1452 Cov.: 32 AF XY: 0.107 AC XY: 7978 AN XY: 74410

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.0977

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0562 Hom.: 134

Bravo AF: 0.126

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.85

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: rs1056189; hg19: chr5-149014418;