5-149620377-C-T

Position:

• chr5-149620377-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001001669.3(ARHGEF37):​c.918C>T​(p.His306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,611,866 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (1 hom.)
• Consequence: ARHGEF37 NM_001001669.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.760

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-149620377-C-T is Benign according to our data. Variant chr5-149620377-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.76 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF37	NM_001001669.3	c.918C>T	p.His306=	synonymous_variant	8/13	ENST00000333677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF37	ENST00000333677.7	c.918C>T	p.His306=	synonymous_variant	8/13	2	NM_001001669.3	P1

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152188 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000706 AC: 174 AN: 246596 Hom.: 1 AF XY: 0.000680 AC XY: 91 AN XY: 133900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00679

Gnomad EAS exome AF: 0.00233

Gnomad SAS exome AF: 0.000231

Gnomad FIN exome AF: 0.000789

Gnomad NFE exome AF: 0.000267

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.000398 AC: 581 AN: 1459560 Hom.: 1 Cov.: 31 AF XY: 0.000395 AC XY: 287 AN XY: 726046

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000900

Gnomad4 ASJ exome AF: 0.00506

Gnomad4 EAS exome AF: 0.00380

Gnomad4 SAS exome AF: 0.000256

Gnomad4 FIN exome AF: 0.000937

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.000862

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152306 Hom.: 1 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74464

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000655 Hom.: 0

Bravo AF: 0.000329

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ARHGEF37: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.0
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs368910887; hg19: chr5-148999940;