5-73773755-C-T

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.476-100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 1,144,480 control chromosomes in the GnomAD database, including 4,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (385 hom., cov: 32)
  • Exomes 𝑓: 0.085 (4242 hom.)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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=-0.86).
• BP6: Variant 5-73773755-C-T is Benign according to our data. Variant chr5-73773755-C-T is described in ClinVar as [Benign]. Clinvar id is 1222419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF28	NM_001177693.2	c.476-100C>T		intron_variant		ENST00000513042.7
ARHGEF28	NM_001080479.3	c.476-100C>T		intron_variant
ARHGEF28	NM_001388076.1	c.182-100C>T		intron_variant
ARHGEF28	NM_001388078.1	c.476-100C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.476-100C>T		intron_variant		5	NM_001177693.2

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9274 AN: 152128 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0497

GnomAD4 exome AF: 0.0850 AC: 84379 AN: 992234 Hom.: 4242 AF XY: 0.0850 AC XY: 41508 AN XY: 488096

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.0335

Gnomad4 ASJ exome AF: 0.0809

Gnomad4 EAS exome AF: 0.000124

Gnomad4 SAS exome AF: 0.0782

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.0790

GnomAD4 genome AF: 0.0609 AC: 9272 AN: 152246 Hom.: 385 Cov.: 32 AF XY: 0.0598 AC XY: 4454 AN XY: 74440

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0401

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.0496

Alfa AF: 0.0817 Hom.: 104

Bravo AF: 0.0569

Asia WGS AF: 0.0250 AC: 87 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.52

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: rs79391401; hg19: chr5-73069580;