chr5-149606436-G-A

Variant names:

• chr5-149606436-G-A
• rs11167472
• NM_001001669.3:c.311-3112G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001669.3(ARHGEF37):​c.311-3112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,964 control chromosomes in the GnomAD database, including 22,392 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 0.54 (22392 hom., cov: 32)
• Consequence: ARHGEF37 NM_001001669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 3 publications found

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]

RNU6-588P (HGNC:47551): (RNA, U6 small nuclear 588, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF37	NM_001001669.3	c.311-3112G>A		intron_variant	Intron 3 of 12	ENST00000333677.7	NP_001001669.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF37	ENST00000333677.7	c.311-3112G>A		intron_variant	Intron 3 of 12	2	NM_001001669.3	ENSP00000328083.6
RNU6-588P	ENST00000410281.1	n.*201C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81728 AN: 151844 Hom.: 22350 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.538 AC: 81826 AN: 151964 Hom.: 22392 Cov.: 32 AF XY: 0.541 AC XY: 40205 AN XY: 74276

African (AFR) AF: 0.517 AC: 21441 AN: 41450

American (AMR) AF: 0.642 AC: 9803 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1682 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3685 AN: 5166

South Asian (SAS) AF: 0.682 AC: 3287 AN: 4820

European-Finnish (FIN) AF: 0.440 AC: 4638 AN: 10548

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35411 AN: 67936

Other (OTH) AF: 0.537 AC: 1133 AN: 2108

Alfa AF: 0.549 Hom.: 4109

Bravo AF: 0.554

Asia WGS AF: 0.731 AC: 2540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.42
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11167472; hg19: chr5-148985999;