5-73684549-T-G

Position:

• chr5-73684549-T-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.-11-292T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,318 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.026 (172 hom., cov: 32)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.202

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=-0.91).
• BP6: Variant 5-73684549-T-G is Benign according to our data. Variant chr5-73684549-T-G is described in ClinVar as [Benign]. Clinvar id is 1249038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF28	NM_001177693.2	c.-11-292T>G		intron_variant		ENST00000513042.7	NP_001171164.1
ARHGEF28	NM_001080479.3	c.-11-292T>G		intron_variant			NP_001073948.2
ARHGEF28	NM_001388076.1	c.-11-292T>G		intron_variant			NP_001375005.1
ARHGEF28	NM_001388078.1	c.-11-292T>G		intron_variant			NP_001375007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.-11-292T>G		intron_variant		5	NM_001177693.2	ENSP00000441436
ARHGEF28	ENST00000296794.10	c.-11-292T>G		intron_variant		5		ENSP00000296794
ARHGEF28	ENST00000509848.5	c.-11-292T>G		intron_variant		4		ENSP00000421859
ARHGEF28	ENST00000545377.5	c.-11-292T>G		intron_variant		5		ENSP00000441913

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3928 AN: 152200 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0258 AC: 3932 AN: 152318 Hom.: 172 Cov.: 32 AF XY: 0.0254 AC XY: 1890 AN XY: 74480

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.000502 Hom.: 0

Bravo AF: 0.0294

Asia WGS AF: 0.00635 AC: 22 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.67

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: rs77528424; hg19: chr5-72980374;