5-149591742-A-G

Position:

• chr5-149591742-A-G

Variant summary

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

The NM_001001669.3(ARHGEF37):​c.-11-6017A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,110 control chromosomes in the GnomAD database, including 34,791 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 0.66 (34791 hom., cov: 32)
• Consequence: ARHGEF37 NM_001001669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF37	NM_001001669.3	c.-11-6017A>G		intron_variant		ENST00000333677.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF37	ENST00000333677.7	c.-11-6017A>G		intron_variant		2	NM_001001669.3	P1
ARHGEF37	ENST00000505810.5	c.-11-6017A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99695 AN: 151992 Hom.: 34728 Cov.: 32

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.656 AC: 99823 AN: 152110 Hom.: 34791 Cov.: 32 AF XY: 0.659 AC XY: 48981 AN XY: 74352

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.629

Alfa AF: 0.529 Hom.: 2575

Bravo AF: 0.688

Asia WGS AF: 0.864 AC: 3001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.58

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: rs7705454; hg19: chr5-148971305;