rs6579746

chr5-149606813-C-G

Variant summary

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

The NM_001001669.3(ARHGEF37):c.311-2735C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,152 control chromosomes in the GnomAD database, including 10,754 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 0.34 (10753 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: ARHGEF37 NM_001001669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF37	NM_001001669.3	c.311-2735C>G		intron_variant		ENST00000333677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF37	ENST00000333677.7	c.311-2735C>G		intron_variant		2	NM_001001669.3	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51362 AN: 152030 Hom.: 10758 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.338 AC: 51352 AN: 152148 Hom.: 10753 Cov.: 32 AF XY: 0.335 AC XY: 24944 AN XY: 74390

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.00501

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.364

Alfa AF: 0.401 Hom.: 1798

Bravo AF: 0.309

Asia WGS AF: 0.131 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.40

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: rs6579746; hg19: chr5-148986376;