5-73919412-G-A

Position:

• chr5-73919412-G-A

Variant summary

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

The NM_001177693.2(ARHGEF28):​c.4948+7837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,154 control chromosomes in the GnomAD database, including 4,041 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 0.16 (4041 hom., cov: 32)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF28	NM_001177693.2	c.4948+7837G>A		intron_variant		ENST00000513042.7	NP_001171164.1
ARHGEF28	NM_001080479.3	c.4949-3675G>A		intron_variant			NP_001073948.2
ARHGEF28	NM_001244364.2	c.4009+7837G>A		intron_variant			NP_001231293.1
ARHGEF28	NM_001388076.1	c.4654+7837G>A		intron_variant			NP_001375005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.4948+7837G>A		intron_variant		5	NM_001177693.2	ENSP00000441436

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24353 AN: 152036 Hom.: 4018 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.161 AC: 24425 AN: 152154 Hom.: 4041 Cov.: 32 AF XY: 0.156 AC XY: 11598 AN XY: 74390

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0478 Hom.: 325

Bravo AF: 0.186

Asia WGS AF: 0.112 AC: 392 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	0.047
DANN	Benign	0.48

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: rs16871023; hg19: chr5-73215237;