rs10160678

Variant names:

• chr11-5261664-C-A
• rs10160678
• ENST00000380259.7:n.*867-6499G>T

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-6499G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,018 control chromosomes in the GnomAD database, including 51,644 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 (51644 hom., cov: 31)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 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.*867-6499G>T		intron_variant	Intron 6 of 7	5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-7150G>T		intron_variant	Intron 1 of 2	3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.871-2888G>T		intron_variant	Intron 4 of 6
ENSG00000239920	ENST00000646569.1	n.59-2127G>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124911 AN: 151900 Hom.: 51587 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.822 AC: 125030 AN: 152018 Hom.: 51644 Cov.: 31 AF XY: 0.818 AC XY: 60781 AN XY: 74296

African (AFR) AF: 0.891 AC: 36933 AN: 41452

American (AMR) AF: 0.850 AC: 12990 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2893 AN: 3470

East Asian (EAS) AF: 0.895 AC: 4632 AN: 5174

South Asian (SAS) AF: 0.819 AC: 3945 AN: 4816

European-Finnish (FIN) AF: 0.679 AC: 7154 AN: 10542

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53755 AN: 67962

Other (OTH) AF: 0.849 AC: 1795 AN: 2114

Alfa AF: 0.804 Hom.: 6115

Bravo AF: 0.837

Asia WGS AF: 0.859 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.81
DANN	Benign	0.30
PhyloP100		-0.98
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: rs10160678; hg19: chr11-5282894;