5-73773756-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001177693.2(ARHGEF28):c.476-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,143,728 control chromosomes in the GnomAD database, including 183,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (30177 hom., cov: 33)
  • Exomes 𝑓: 0.55 (153054 hom.)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-73773756-A-G is Benign according to our data. Variant chr5-73773756-A-G is described in ClinVar as [Benign]. Clinvar id is 1277651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF28	NM_001177693.2	c.476-99A>G		intron_variant		ENST00000513042.7
ARHGEF28	NM_001080479.3	c.476-99A>G		intron_variant
ARHGEF28	NM_001388076.1	c.182-99A>G		intron_variant
ARHGEF28	NM_001388078.1	c.476-99A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.476-99A>G		intron_variant		5	NM_001177693.2

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94107 AN: 152032 Hom.: 30122 Cov.: 33

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.604

GnomAD4 exome AF: 0.551 AC: 546787 AN: 991578 Hom.: 153054 AF XY: 0.550 AC XY: 267843 AN XY: 487364

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.619 AC: 94221 AN: 152150 Hom.: 30177 Cov.: 33 AF XY: 0.617 AC XY: 45863 AN XY: 74372

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.603

Alfa AF: 0.579 Hom.: 5946

Bravo AF: 0.632

Asia WGS AF: 0.470 AC: 1637 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.16
Dann	Benign	0.61

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: rs4704097; hg19: chr5-73069581;