Variant chr11-5248356-A-AG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_000559.3(HBG1):c.*2_*3insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 151,530 control chromosomes in the GnomAD database, including 51,501 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.82 ( 51501 hom., cov: 30)

Exomes 𝑓: 0.79 ( 453941 hom. )

Failed GnomAD Quality Control

Consequence

HBG1
NM_000559.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.14

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 11-5248356-A-AG is Benign according to our data. Variant chr11-5248356-A-AG is described in ClinVar as [Benign]. Clinvar id is 3059280.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBG1	NM_000559.3 linkuse as main transcript	c.2_3insC		3_prime_UTR_variant	3/3	ENST00000330597.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBG1	ENST00000330597.5 linkuse as main transcript	c.2_3insC		3_prime_UTR_variant	3/3	1	NM_000559.3	P1
HBG1	ENST00000648735.1 linkuse as main transcript	n.1377_1378insC		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.822

AC:

124525

AN:

151412

Hom.:

51443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.850

Gnomad ASJ

AF:

0.837

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.820

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.846

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.790

AC:

1146820

AN:

1450844

Hom.:

453941

Cov.:

AF XY:

0.790

AC XY:

570627

AN XY:

722016

show subpopulations

Gnomad4 AFR exome

AF:

0.894

Gnomad4 AMR exome

AF:

0.830

Gnomad4 ASJ exome

AF:

0.833

Gnomad4 EAS exome

AF:

0.870

Gnomad4 SAS exome

AF:

0.813

Gnomad4 FIN exome

AF:

0.704

Gnomad4 NFE exome

AF:

0.783

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.823

AC:

124645

AN:

151530

Hom.:

51501

Cov.:

AF XY:

0.818

AC XY:

60540

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.891

Gnomad4 AMR

AF:

0.850

Gnomad4 ASJ

AF:

0.837

Gnomad4 EAS

AF:

0.895

Gnomad4 SAS

AF:

0.820

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.848

Alfa

AF:

0.728

Hom.:

4892

Asia WGS

AF:

0.860

AC:

2989

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HBG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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