chr11-5248569-A-C

Position:

• chr11-5248569-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000559.3(HBG1):​c.316-82T>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 150,062 control chromosomes in the GnomAD database, including 50,217 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 (50217 hom., cov: 28)
  • Exomes 𝑓: 0.79 (347616 hom.)
  • Failed GnomAD Quality Control
• Consequence: HBG1 NM_000559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

ENSG00000284931 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBG1	NM_000559.3	c.316-82T>G		intron_variant		ENST00000330597.5	NP_000550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBG1	ENST00000330597.5	c.316-82T>G		intron_variant		1	NM_000559.3	ENSP00000327431.4
ENSG00000284931	ENST00000642908.1	c.316-82T>G		intron_variant				ENSP00000495346.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 122420 AN: 149948 Hom.: 50165 Cov.: 28

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.842

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.789 AC: 878099 AN: 1112438 Hom.: 347616 AF XY: 0.790 AC XY: 446984 AN XY: 565632

Gnomad4 AFR exome AF: 0.869

Gnomad4 AMR exome AF: 0.829

Gnomad4 ASJ exome AF: 0.831

Gnomad4 EAS exome AF: 0.867

Gnomad4 SAS exome AF: 0.813

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.807

GnomAD4 genome AF: 0.817 AC: 122532 AN: 150062 Hom.: 50217 Cov.: 28 AF XY: 0.812 AC XY: 59572 AN XY: 73320

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.844

Alfa AF: 0.730 Hom.: 1980

Bravo AF: 0.832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs28440105; hg19: chr11-5269799;