Variant 6-146685746-T-C 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.1229T>C(p.Ile410Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,529,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ADGB
NM_024694.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.694

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=0.047969162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGB	NM_024694.4 linkuse as main transcript	c.1229T>C	p.Ile410Thr	missense_variant	10/36	ENST00000397944.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGB	ENST00000397944.8 linkuse as main transcript	c.1229T>C	p.Ile410Thr	missense_variant	10/36	5	NM_024694.4	P4	Q8N7X0-1
ADGB	ENST00000493950.6 linkuse as main transcript	c.*339T>C		3_prime_UTR_variant, NMD_transcript_variant	8/32	1
ADGB	ENST00000681847.1 linkuse as main transcript	c.1229T>C	p.Ile410Thr	missense_variant	10/36			A2
ADGB	ENST00000326929.8 linkuse as main transcript	n.1270T>C		non_coding_transcript_exon_variant	10/18	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

137668

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

73124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1377870

Hom.:

Cov.:

AF XY:

0.0000177

AC XY:

AN XY:

679332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000318

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000849

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

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

Oct 20, 2023

The c.1229T>C (p.I410T) alteration is located in exon 10 (coding exon 10) of the ADGB gene. This alteration results from a T to C substitution at nucleotide position 1229, causing the isoleucine (I) at amino acid position 410 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.75

Cadd

Benign

0.15

Dann

Benign

0.54

DEOGEN2

Benign

0.00047

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.54

M_CAP

Benign

0.0032

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

1.1

REVEL

Benign

0.071

Sift

Benign

0.49

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.041

MutPred

0.40

Loss of stability (P = 0.0049);

MVP

0.014

ClinPred

0.035

GERP RS

-7.3

Varity_R

0.037

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

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