Variant 7-905180-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006869.4(ADAP1):c.389-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,609,926 control chromosomes in the GnomAD database, including 153 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 0.0090 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 131 hom. )

Consequence

ADAP1
NM_006869.4 splice_region, intron

Scores

Splicing: ADA: 0.00006454

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.719

Variant links:

Genes affected

ADAP1 (HGNC:16486): (ArfGAP with dual PH domains 1) Enables GTPase activator activity. Involved in regulation of GTPase activity. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADAP1 links:

ADAP1 (HGNC:):

ADAP1 links:

COX19 (HGNC:28074): (cytochrome c oxidase assembly factor COX19) COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

COX19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-905180-G-C is Benign according to our data. Variant chr7-905180-G-C is described in ClinVar as [Benign]. Clinvar id is 774872.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-905180-G-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAP1	NM_006869.4 linkuse as main transcript	c.389-8C>G		splice_region_variant, intron_variant		ENST00000265846.10	NP_006860.2	O75689-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAP1	ENST00000265846.10 linkuse as main transcript	c.389-8C>G		splice_region_variant, intron_variant		1	NM_006869.4	ENSP00000265846.5		O75689-1

Frequencies

GnomAD3 genomes

AF:

0.00906

AC:

1377

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0699

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00716

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00969

AC:

2398

AN:

247566

Hom.:

AF XY:

0.00908

AC XY:

1222

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.0608

Gnomad NFE exome

AF:

0.00628

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00729

AC:

10630

AN:

1457750

Hom.:

131

Cov.:

AF XY:

0.00695

AC XY:

5038

AN XY:

725360

show subpopulations

Gnomad4 AFR exome

AF:

0.000927

Gnomad4 AMR exome

AF:

0.00977

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.0585

Gnomad4 NFE exome

AF:

0.00608

Gnomad4 OTH exome

AF:

0.00625

GnomAD4 genome

AF:

0.00904

AC:

1376

AN:

152176

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

847

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0699

Gnomad4 NFE

AF:

0.00716

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00552

Hom.:

Bravo

AF:

0.00442

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.61

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.012

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