dbSNP rs11036415: HBD:c.-29+1898T>G (chr11-5241552-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000643122.1(HBD):c.-29+1898T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,058 control chromosomes in the GnomAD database, including 50,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 50864 hom., cov: 30)

Exomes 𝑓: 0.81 ( 17 hom. )

Consequence

HBD
ENST00000643122.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

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 links:

ENSG00000290652 (HGNC:):

ENSG00000290652 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1 link	c.-29+1898T>G		intron_variant	Intron 1 of 3			ENSP00000494708.1		P02042
ENSG00000290652	ENST00000454892.2 link	n.1003T>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.817

AC:

124108

AN:

151886

Hom.:

50820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.818

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.863

Gnomad ASJ

AF:

0.869

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.832

Gnomad FIN

AF:

0.683

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.857

GnomAD4 exome

AF:

0.815

AC:

AN:

Hom.:

Cov.:

AF XY:

0.813

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.833

Gnomad4 OTH exome

AF:

0.833

GnomAD4 genome

AF:

0.817

AC:

124214

AN:

152004

Hom.:

50864

Cov.:

AF XY:

0.813

AC XY:

60417

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.818

Gnomad4 AMR

AF:

0.863

Gnomad4 ASJ

AF:

0.869

Gnomad4 EAS

AF:

0.898

Gnomad4 SAS

AF:

0.833

Gnomad4 FIN

AF:

0.683

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.860

Alfa

AF:

0.816

Hom.:

10270

Bravo

AF:

0.825

Asia WGS

AF:

0.865

AC:

3008

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.48

DANN

Benign

0.40

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over