dbSNP rs33924825: HBG1:p.Glu7Gln (chr11-5249786-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000559.3(HBG1):c.19G>C(p.Glu7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 5)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

HBG1
NM_000559.3 missense

Scores

Clinical Significance

other no assertion criteria provided O:1

Conservation

PhyloP100: 1.45

Publications

2 publications found

Variant links:

Genes affected

HBG1 (HGNC:4831): (hemoglobin subunit gamma 1) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

HBG1 Gene-Disease associations (from GenCC):

hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
delta-beta-thalassemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HBG1 links:

ENSG00000284931 (HGNC:):

ENSG00000284931 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32361776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBG1	NM_000559.3 link	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 3	ENST00000330597.5	NP_000550.2	P69891D9YZU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBG1	ENST00000330597.5 link	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 3	1	NM_000559.3	ENSP00000327431.4		P69891
ENSG00000284931	ENST00000642908.1 link	c.316-1299G>C		intron_variant	Intron 2 of 2			ENSP00000495346.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000329

AC:

AN:

303734

Hom.:

Cov.:

AF XY:

0.00000624

AC XY:

AN XY:

160330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8754

American (AMR)

AF:

0.00

AC:

AN:

13956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9020

East Asian (EAS)

AF:

0.00

AC:

AN:

18244

South Asian (SAS)

AF:

0.00

AC:

AN:

36122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1202

European-Non Finnish (NFE)

AF:

0.00000556

AC:

AN:

179824

Other (OTH)

AF:

0.00

AC:

AN:

16770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HEMOGLOBIN F (PORDENONE)

Other:1

Jul 15, 2011

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

Benign

0.089

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.83

T;.

M_CAP

Benign

0.047

MetaRNN

Benign

0.32

T;T

MetaSVM

Uncertain

0.51

PhyloP100

1.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

N;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.0010

D;.

Sift4G

Benign

0.14

T;.

Polyphen

0.98

D;.

Vest4

0.18

MutPred

0.51

Loss of ubiquitination at K9 (P = 0.0573);Loss of ubiquitination at K9 (P = 0.0573);

MVP

0.93

MPC

1.9

ClinPred

0.80

GERP RS

2.8

PromoterAI

-0.0014

Neutral

(source)

gMVP

0.21

Mutation Taster

=30/70

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over