dbSNP rs34012192: HBD:p.Gly17Arg (chr11-5234385-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000519.4(HBD):c.49G>C(p.Gly17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,614,036 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

HBD
NM_000519.4 missense

Scores

Clinical Significance

other no assertion criteria provided O:2

Conservation

PhyloP100: -1.18

Publications

1 publications found

Variant links:

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

HBD Gene-Disease associations (from GenCC):

delta-beta-thalassemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HBD links:

ENSG00000298932 (HGNC:):

ENSG00000298932 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012547195).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBD	NM_000519.4 link	c.49G>C	p.Gly17Arg	missense_variant	Exon 1 of 3	ENST00000650601.1	NP_000510.1	P02042A0N071

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000650601.1 link	c.49G>C	p.Gly17Arg	missense_variant	Exon 1 of 3		NM_000519.4	ENSP00000497529.1		P02042

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00954

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000748

AC:

188

AN:

251240

AF XY:

0.000604

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000295

AC:

431

AN:

1461774

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

185

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0109

AC:

365

AN:

33468

American (AMR)

AF:

0.000514

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111920

Other (OTH)

AF:

0.000530

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00275

AC:

419

AN:

152262

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00956

AC:

397

AN:

41540

American (AMR)

AF:

0.00131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.00301

ESP6500AA

AF:

0.00977

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000914

AC:

111

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: other

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HEMOGLOBIN B(2)

Other:1

Dec 12, 2017

OMIM

Significance:other

Review Status:no assertion criteria provided

Collection Method:literature only

- -

HEMOGLOBIN A(2)-PRIME

Other:1

Dec 12, 2017

OMIM

Significance:other

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Benign

5.7

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.021

T;T;T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.67

T;.;.;T;T;T

MetaRNN

Benign

0.013

T;T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.0

.;M;M;M;.;.

PhyloP100

-1.2

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.5

D;.;D;.;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0020

D;.;D;.;D;D

Sift4G

Uncertain

0.010

D;.;D;.;D;.

Polyphen

0.042

.;B;B;B;.;.

Vest4

0.43

MVP

0.62

MPC

0.012

ClinPred

0.082

GERP RS

-9.2

PromoterAI

0.019

Neutral

(source)

Varity_R

0.43

gMVP

0.71

Mutation Taster

=46/54

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over