chr5-73853291-T-C

Position:

• chr5-73853291-T-C

Variant summary

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

The NM_001177693.2(ARHGEF28):​c.1790+599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,292 control chromosomes in the GnomAD database, including 449 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 0.073 (449 hom., cov: 33)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF28	NM_001177693.2	c.1790+599T>C		intron_variant		ENST00000513042.7	NP_001171164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.1790+599T>C		intron_variant		5	NM_001177693.2	ENSP00000441436.1

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11135 AN: 152174 Hom.: 449 Cov.: 33

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.0732 AC: 11148 AN: 152292 Hom.: 449 Cov.: 33 AF XY: 0.0725 AC XY: 5395 AN XY: 74464

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0767 Hom.: 654

Bravo AF: 0.0702

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.70

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: rs17553316; hg19: chr5-73149116;