chr5-73684549-T-C

Variant names:

• chr5-73684549-T-C
• rs77528424
• NM_001177693.2:c.-11-292T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001177693.2(ARHGEF28):​c.-11-292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 32)
• Consequence: ARHGEF28 NM_001177693.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF28	NM_001177693.2	c.-11-292T>C		intron_variant	Intron 1 of 35	ENST00000513042.7	NP_001171164.1
ARHGEF28	NM_001080479.3	c.-11-292T>C		intron_variant	Intron 1 of 36		NP_001073948.2
ARHGEF28	NM_001388078.1	c.-11-292T>C		intron_variant	Intron 1 of 34		NP_001375007.1
ARHGEF28	NM_001388076.1	c.-11-292T>C		intron_variant	Intron 1 of 34		NP_001375005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF28	ENST00000513042.7	c.-11-292T>C		intron_variant	Intron 1 of 35	5	NM_001177693.2	ENSP00000441436.1
ARHGEF28	ENST00000545377.5	c.-11-292T>C		intron_variant	Intron 1 of 36	5		ENSP00000441913.1
ARHGEF28	ENST00000296794.10	c.-11-292T>C		intron_variant	Intron 1 of 34	5		ENSP00000296794.6
ARHGEF28	ENST00000509848.5	c.-11-292T>C		intron_variant	Intron 2 of 4	4		ENSP00000421859.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.65

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;