NM_000559.3:c.316-214C>G

Variant names:

• chr11-5248701-G-C
• rs2187608
• NM_000559.3:c.316-214C>G

Variant summary

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

The NM_000559.3(HBG1):​c.316-214C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 150,532 control chromosomes in the GnomAD database, including 6,489 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 0.28 (6489 hom., cov: 29)
• Consequence: HBG1 NM_000559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBG1	NM_000559.3	c.316-214C>G		intron_variant	Intron 2 of 2	ENST00000330597.5	NP_000550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBG1	ENST00000330597.5	c.316-214C>G		intron_variant	Intron 2 of 2	1	NM_000559.3	ENSP00000327431.4
ENSG00000284931	ENST00000642908.1	c.316-214C>G		intron_variant	Intron 2 of 2			ENSP00000495346.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42516 AN: 150414 Hom.: 6483 Cov.: 29

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.283 AC: 42550 AN: 150532 Hom.: 6489 Cov.: 29 AF XY: 0.276 AC XY: 20323 AN XY: 73574

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.281

Alfa AF: 0.171 Hom.: 352

Bravo AF: 0.281

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.53

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: rs2187608; hg19: chr11-5269931; COSMIC: COSV57964852; COSMIC: COSV57964852;