Variant chr6-146656764-T-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_024694.4(ADGB):c.403-7T>C 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 0.00917 in 1,511,436 control chromosomes in the GnomAD database, including 87 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 82 hom. )

Consequence

ADGB
NM_024694.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006450

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0380

Variant links:

Genes affected

ADGB (HGNC:21212): (androglobin) Predicted to enable calcium-dependent cysteine-type endopeptidase activity; heme binding activity; and oxygen binding activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

ADGB 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=-0.83).

BP6

Variant 6-146656764-T-C is Benign according to our data. Variant chr6-146656764-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656976.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGB	NM_024694.4 linkuse as main transcript	c.403-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000397944.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGB	ENST00000397944.8 linkuse as main transcript	c.403-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_024694.4	P4	Q8N7X0-1

Frequencies

GnomAD3 genomes

AF:

0.00634

AC:

965

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00955

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00734

AC:

956

AN:

130318

Hom.:

AF XY:

0.00798

AC XY:

539

AN XY:

67568

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00286

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00795

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.00930

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.00949

AC:

12898

AN:

1359124

Hom.:

Cov.:

AF XY:

0.00956

AC XY:

6372

AN XY:

666566

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00417

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00955

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00767

GnomAD4 genome

AF:

0.00633

AC:

964

AN:

152312

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

471

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.00955

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00735

Hom.:

Bravo

AF:

0.00502

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ADGB: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

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