rs9293611

chr5-73758248-A-T

Variant summary

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

The NM_001177693.2(ARHGEF28):c.475+5046A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,088 control chromosomes in the GnomAD database, including 12,815 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 0.38 (12815 hom., cov: 32)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

ARHGEF28 (HGNC:30322): (Rho guanine nucleotide exchange factor 28) This gene encodes a member of the Rho guanine nucleotide exchange factor family. The encoded protein interacts with low molecular weight neurofilament mRNA and may be involved in the formation of amyotrophic lateral sclerosis neurofilament aggregates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF28	NM_001177693.2	c.475+5046A>T		intron_variant		ENST00000513042.7
ARHGEF28	NM_001080479.3	c.475+5046A>T		intron_variant
ARHGEF28	NM_001388076.1	c.181+8264A>T		intron_variant
ARHGEF28	NM_001388078.1	c.475+5046A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.475+5046A>T		intron_variant		5	NM_001177693.2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57170 AN: 151970 Hom.: 12775 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.377 AC: 57264 AN: 152088 Hom.: 12815 Cov.: 32 AF XY: 0.371 AC XY: 27613 AN XY: 74340

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.356

Alfa AF: 0.342 Hom.: 1234

Bravo AF: 0.385

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.45
Dann	Benign	0.65

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: rs9293611; hg19: chr5-73054073; COSMIC: COSV55269576;