rs376619433

Variant names:

• chr11-73308662-C-A
• rs376619433
• NM_014786.4:c.24C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-73308662-C-A
• chr11-73308662-C-G
• chr11-73308662-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014786.4(ARHGEF17):​c.24C>A​(p.Pro8Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,360,822 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. Synonymous variant affecting the same amino acid position (i.e. P8P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: ARHGEF17 NM_014786.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• Publications: 0 publications found

Genes affected

ARHGEF17 (HGNC:21726): (Rho guanine nucleotide exchange factor 17) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within actin cytoskeleton organization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF17-AS1 (HGNC:55485): (ARHGEF17 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.845 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF17	NM_014786.4	MANE Select	c.24C>A	p.Pro8Pro	synonymous	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.690+10G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF17	ENST00000263674.4	TSL:1 MANE Select	c.24C>A	p.Pro8Pro	synonymous	Exon 1 of 21	ENSP00000263674.3	Q96PE2
	ARHGEF17	ENST00000914587.1		c.24C>A	p.Pro8Pro	synonymous	Exon 1 of 20	ENSP00000584647.1
	ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.690+10G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000924 AC: 1 AN: 108246 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000347

GnomAD4 exome AF: 0.00000441 AC: 6 AN: 1360822 Hom.: 0 Cov.: 30 AF XY: 0.00000595 AC XY: 4 AN XY: 672776

African (AFR) AF: 0.00 AC: 0 AN: 27490

American (AMR) AF: 0.00 AC: 0 AN: 31986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23784

East Asian (EAS) AF: 0.00 AC: 0 AN: 30110

South Asian (SAS) AF: 0.00 AC: 0 AN: 76074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4812

European-Non Finnish (NFE) AF: 0.00000563 AC: 6 AN: 1066342

Other (OTH) AF: 0.00 AC: 0 AN: 56164

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		0.84
PromoterAI		0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs376619433; hg19: chr11-73019707;