rs793516

Variant names:

• chr10-97228228-G-T
• rs793516
• NM_032900.6:c.1474+919C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032900.6(ARHGAP19):​c.1474+919C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,036 control chromosomes in the GnomAD database, including 6,380 homozygotes. 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 0.29 (6380 hom., cov: 32)
• Consequence: ARHGAP19 NM_032900.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 7 publications found

Genes affected

ARHGAP19 (HGNC:23724): (Rho GTPase activating protein 19) Members of the ARHGAP family, such as ARHGAP19, encode negative regulators of Rho GTPases (see RHOA; MIM 165390), which are involved in cell migration, proliferation, and differentiation, actin remodeling, and G1 cell cycle progression (Lv et al., 2007 [PubMed 17454002]).[supplied by OMIM, Mar 2008]

ARHGAP19-SLIT1 (HGNC:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

LOC105378447 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP19	NM_032900.6	c.1474+919C>A		intron_variant	Intron 11 of 11	ENST00000358531.9	NP_116289.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP19	ENST00000358531.9	c.1474+919C>A		intron_variant	Intron 11 of 11	1	NM_032900.6	ENSP00000351333.4
ARHGAP19-SLIT1	ENST00000479633.2	n.1474+919C>A		intron_variant	Intron 11 of 14	2		ENSP00000473567.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43504 AN: 151918 Hom.: 6377 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.286 AC: 43537 AN: 152036 Hom.: 6380 Cov.: 32 AF XY: 0.287 AC XY: 21293 AN XY: 74296

African (AFR) AF: 0.245 AC: 10180 AN: 41468

American (AMR) AF: 0.268 AC: 4094 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3468

East Asian (EAS) AF: 0.123 AC: 639 AN: 5188

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4814

European-Finnish (FIN) AF: 0.341 AC: 3598 AN: 10546

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21980 AN: 67976

Other (OTH) AF: 0.254 AC: 535 AN: 2108

Alfa AF: 0.308 Hom.: 924

Bravo AF: 0.278

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs793516; hg19: chr10-98987985;