Variant 6-146676355-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024694.4(ADGB):c.1130A>T(p.Asp377Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,549,658 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

ADGB
NM_024694.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034286708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGB	NM_024694.4 linkuse as main transcript	c.1130A>T	p.Asp377Val	missense_variant	9/36	ENST00000397944.8	NP_078970.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGB	ENST00000397944.8 linkuse as main transcript	c.1130A>T	p.Asp377Val	missense_variant	9/36	5	NM_024694.4	ENSP00000381036	P4	Q8N7X0-1
ADGB	ENST00000493950.6 linkuse as main transcript	c.*240A>T		3_prime_UTR_variant, NMD_transcript_variant	7/32	1		ENSP00000430244
ADGB	ENST00000681847.1 linkuse as main transcript	c.1130A>T	p.Asp377Val	missense_variant	9/36			ENSP00000505524	A2
ADGB	ENST00000326929.8 linkuse as main transcript	n.1171A>T		non_coding_transcript_exon_variant	9/18	2

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000400

AC:

AN:

155182

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

82264

show subpopulations

Gnomad AFR exome

AF:

0.000507

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000366

Gnomad OTH exome

AF:

0.00139

GnomAD4 exome

AF:

0.000303

AC:

423

AN:

1397378

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

205

AN XY:

689186

show subpopulations

Gnomad4 AFR exome

AF:

0.000444

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0000398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000760

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000276

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000637

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000786

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000122

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.1130A>T (p.D377V) alteration is located in exon 9 (coding exon 9) of the ADGB gene. This alteration results from a A to T substitution at nucleotide position 1130, causing the aspartic acid (D) at amino acid position 377 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.20

Sift

Benign

0.16

Sift4G

Uncertain

0.0090

Polyphen

0.97

Vest4

0.22

MVP

0.17

ClinPred

0.044

GERP RS

5.5

Varity_R

0.22

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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