Variant chr1-17622992-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018125.4(ARHGEF10L):c.1021-4G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,610,694 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 147 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 134 hom. )

Consequence

ARHGEF10L
NM_018125.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003909

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.338

Variant links:

Genes affected

ARHGEF10L (HGNC:25540): (Rho guanine nucleotide exchange factor 10 like) This gene belongs to the RhoGEF subfamily of RhoGTPases. Members of this subfamily are activated by specific guanine nucleotide exchange factors (GEFs) and are involved in signal transduction. The encoded protein shows cytosolic distribution. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2016]

ARHGEF10L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-17622992-G-T is Benign according to our data. Variant chr1-17622992-G-T is described in ClinVar as [Benign]. Clinvar id is 782906.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10L	NM_018125.4 linkuse as main transcript	c.1021-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361221.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ARHGEF10L	ENST00000361221.8 linkuse as main transcript	c.1021-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_018125.4	A1	Q9HCE6-1
ARHGEF10L	ENST00000375415.5 linkuse as main transcript	c.904-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		P4	Q9HCE6-2
ARHGEF10L	ENST00000375408.7 linkuse as main transcript	c.355-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		A1
ARHGEF10L	ENST00000469726.5 linkuse as main transcript	n.1301-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3569

AN:

152196

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0815

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00609

AC:

1505

AN:

247112

Hom.:

AF XY:

0.00450

AC XY:

602

AN XY:

133854

show subpopulations

Gnomad AFR exome

AF:

0.0843

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00235

AC:

3433

AN:

1458380

Hom.:

134

Cov.:

AF XY:

0.00199

AC XY:

1443

AN XY:

725474

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.00411

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.0235

AC:

3579

AN:

152314

Hom.:

147

Cov.:

AF XY:

0.0226

AC XY:

1687

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0815

Gnomad4 AMR

AF:

0.00836

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0264

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.71

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.018

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over