rs6579746

Variant names:

• chr5-149606813-C-G
• rs6579746
• NM_001001669.3:c.311-2735C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-149606813-C-G
• chr5-149606813-C-T

Variant summary

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

The NM_001001669.3(ARHGEF37):​c.311-2735C>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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ARHGEF37	NM_001001669.3	c.311-2735C>G		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.311-2735C>G		intron_variant	Intron 3 of 12	2	NM_001001669.3	ENSP00000328083.6
RNU6-588P	ENST00000410281.1	n.-72G>C		upstream_gene_variant		6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.124 AC: 5154 AN: 41534

American (AMR) AF: 0.303 AC: 4636 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1587 AN: 3468

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5192

South Asian (SAS) AF: 0.281 AC: 1356 AN: 4826

European-Finnish (FIN) AF: 0.519 AC: 5488 AN: 10574

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31908 AN: 67952

Other (OTH) AF: 0.364 AC: 767 AN: 2110

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
PhyloP100		0.41
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: rs6579746; hg19: chr5-148986376;