rs10837707

Variant names:

• chr11-5265578-T-C
• rs10837707
• ENST00000380259.7:n.*867-10413A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380259.7(ENSG00000239920):​n.*867-10413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,818 control chromosomes in the GnomAD database, including 15,277 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 (15277 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 1 publications found

Genes affected

ENSG00000239920 (HGNC:):

HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) 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]

HBG2 Gene-Disease associations (from GenCC):

• hemoglobinopathy Toms River

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cyanosis, transient neonatal

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 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
ENSG00000239920	ENST00000380259.7	n.*867-10413A>G		intron_variant	Intron 6 of 7	5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-11064A>G		intron_variant	Intron 1 of 2	3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.870+2792A>G		intron_variant	Intron 4 of 6
ENSG00000239920	ENST00000646569.1	n.59-6041A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64702 AN: 151700 Hom.: 15265 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.486

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.427 AC: 64754 AN: 151818 Hom.: 15277 Cov.: 32 AF XY: 0.433 AC XY: 32101 AN XY: 74206

African (AFR) AF: 0.233 AC: 9660 AN: 41388

American (AMR) AF: 0.570 AC: 8690 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2076 AN: 3468

East Asian (EAS) AF: 0.776 AC: 4004 AN: 5162

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4820

European-Finnish (FIN) AF: 0.450 AC: 4743 AN: 10546

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31294 AN: 67866

Other (OTH) AF: 0.489 AC: 1030 AN: 2108

Alfa AF: 0.185 Hom.: 1820

Bravo AF: 0.424

Asia WGS AF: 0.592 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.5
DANN	Benign	0.94
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10837707; hg19: chr11-5286808;