Variant 17-1007161-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021962.5(ABR):c.2490+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 878,456 control chromosomes in the GnomAD database, including 58,750 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 0.39 ( 10432 hom., cov: 27)

Exomes 𝑓: 0.28 ( 48318 hom. )

Consequence

ABR
NM_021962.5 splice_region, intron

Scores

Splicing: ADA: 0.0009631

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.152

Variant links:

Genes affected

ABR (HGNC:81): (ABR activator of RhoGEF and GTPase) This gene encodes a protein that is similar to the protein encoded by the breakpoint cluster region gene located on chromosome 22. The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding proteins. Functional studies in mice determined that this protein plays a role in vestibular morphogenesis. Alternatively spliced transcript variants have been reported for this gene. [provided by RefSeq, Feb 2012]

ABR links:

ABR (HGNC:):

ABR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-1007161-G-A is Benign according to our data. Variant chr17-1007161-G-A is described in ClinVar as [Benign]. Clinvar id is 768810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABR	NM_021962.5 linkuse as main transcript	c.2490+4C>T		splice_region_variant, intron_variant		ENST00000302538.10	NP_068781.2	Q12979-1Q6ZT60B7Z7Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABR	ENST00000302538.10 linkuse as main transcript	c.2490+4C>T		splice_region_variant, intron_variant		1	NM_021962.5	ENSP00000303909.5		Q12979-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

54003

AN:

139618

Hom.:

10431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.436

GnomAD3 exomes

AF:

0.212

AC:

26971

AN:

127256

Hom.:

5066

AF XY:

0.200

AC XY:

13255

AN XY:

66298

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.282

AC:

208475

AN:

738722

Hom.:

48318

Cov.:

AF XY:

0.292

AC XY:

111159

AN XY:

380666

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.416

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.327

GnomAD4 genome

AF:

0.387

AC:

54021

AN:

139734

Hom.:

10432

Cov.:

AF XY:

0.384

AC XY:

26118

AN XY:

67998

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.431

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.436

Alfa

AF:

0.412

Hom.:

2711

Asia WGS

AF:

0.187

AC:

595

AN:

3172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.6

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00096

dbscSNV1_RF

Benign

0.068

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