dbSNP rs2242436: ARHGAP45:c.-80C>A (chr19-1065946-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000539243.6(ARHGAP45):c.-80C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,908 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: not found (cov: 34)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

ARHGAP45
ENST00000539243.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.26

Publications

15 publications found

Variant links:

Genes affected

ARHGAP45 (HGNC:17102): (Rho GTPase activating protein 45) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP45 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
ARHGAP45	NM_001258328.4 link	c.-80C>A	upstream_gene_variant	NP_001245257.1	Q92619-2
ARHGAP45	XM_047438545.1 link	c.-80C>A	upstream_gene_variant	XP_047294501.1
ARHGAP45	XM_047438546.1 link	c.-1047C>A	upstream_gene_variant	XP_047294502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000539243.6 link	c.-80C>A		5_prime_UTR_variant	Exon 1 of 23	2		ENSP00000439601.1		Q92619-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.51e-7

AC:

AN:

1331908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30142

American (AMR)

AF:

0.00

AC:

AN:

29574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21706

East Asian (EAS)

AF:

0.00

AC:

AN:

35326

South Asian (SAS)

AF:

0.00

AC:

AN:

71612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3896

European-Non Finnish (NFE)

AF:

9.50e-7

AC:

AN:

1052602

Other (OTH)

AF:

0.00

AC:

AN:

55488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

4201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.38

PhyloP100

-4.3

PromoterAI

-0.10

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over