rs916111

Variant names:

• chr11-5248113-T-A
• rs916111
• NM_000559.3:c.*246A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5248113-T-A
• chr11-5248113-T-G

Variant summary

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

The NM_000559.3(HBG1):​c.*246A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 513,726 control chromosomes in the GnomAD database, including 60,838 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 0.43 (15347 hom., cov: 33)
  • Exomes 𝑓: 0.49 (45491 hom.)
• Consequence: HBG1 NM_000559.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689

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 = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBG1	NM_000559.3	c.*246A>T		downstream_gene_variant		ENST00000330597.5	NP_000550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBG1	ENST00000330597.5	c.*246A>T		downstream_gene_variant		1	NM_000559.3	ENSP00000327431.4
ENSG00000284931	ENST00000642908.1	c.*246A>T		downstream_gene_variant				ENSP00000495346.1
ENSG00000284931	ENST00000647543.1	c.*246A>T		downstream_gene_variant				ENSP00000496470.1
HBG1	ENST00000648735.1	n.*157A>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64574 AN: 151906 Hom.: 15333 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.492 AC: 178087 AN: 361702 Hom.: 45491 Cov.: 4 AF XY: 0.496 AC XY: 95877 AN XY: 193368

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.425 AC: 64628 AN: 152024 Hom.: 15347 Cov.: 33 AF XY: 0.432 AC XY: 32059 AN XY: 74284

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.488

Alfa AF: 0.430 Hom.: 1838

Bravo AF: 0.422

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs916111; hg19: chr11-5269343;