Variant 6-146691251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024694.4(ADGB):c.1447C>T(p.Arg483Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000246 in 1,545,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ADGB
NM_024694.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4156079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGB	NM_024694.4 linkuse as main transcript	c.1447C>T	p.Arg483Cys	missense_variant	11/36	ENST00000397944.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGB	ENST00000397944.8 linkuse as main transcript	c.1447C>T	p.Arg483Cys	missense_variant	11/36	5	NM_024694.4	P4	Q8N7X0-1
ADGB	ENST00000493950.6 linkuse as main transcript	c.*557C>T		3_prime_UTR_variant, NMD_transcript_variant	9/32	1
ADGB	ENST00000681847.1 linkuse as main transcript	c.1447C>T	p.Arg483Cys	missense_variant	11/36			A2
ADGB	ENST00000326929.8 linkuse as main transcript	n.1488C>T		non_coding_transcript_exon_variant	11/18	2

Frequencies

GnomAD3 genomes

AF:

0.0000942

AC:

AN:

148598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000701

AC:

AN:

156942

Hom.:

AF XY:

0.0000846

AC XY:

AN XY:

82702

show subpopulations

Gnomad AFR exome

AF:

0.000730

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000927

Gnomad SAS exome

AF:

0.0000441

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1396522

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

688754

show subpopulations

Gnomad4 AFR exome

AF:

0.000319

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000742

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000942

AC:

AN:

148598

Hom.:

Cov.:

AF XY:

0.0000692

AC XY:

AN XY:

72266

show subpopulations

Gnomad4 AFR

AF:

0.000351

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

ExAC

AF:

0.000117

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

Apr 04, 2023

The c.1447C>T (p.R483C) alteration is located in exon 11 (coding exon 11) of the ADGB gene. This alteration results from a C to T substitution at nucleotide position 1447, causing the arginine (R) at amino acid position 483 to be replaced by a cysteine (C). 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.020

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.035

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.67

MVP

0.32

ClinPred

0.64

GERP RS

4.5

Varity_R

0.38

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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