rs281860601

Variant names:

• chr11-5249971-G-A
• rs281860601
• ENST00000642908.1:c.316-1484C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5249971-G-A
• chr11-5249971-G-C
• chr11-5249971-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP5 BP4

The ENST00000642908.1(ENSG00000284931):​c.316-1484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.0000095 (0 hom., cov: 12)
• Consequence: ENSG00000284931 ENST00000642908.1 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.15
• Publications: 1 publications found

Genes affected

ENSG00000284931 (HGNC:):

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]

HBG1 Gene-Disease associations (from GenCC):

• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• delta-beta-thalassemia

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP5: Variant 11-5249971-G-A is Pathogenic according to our data. Variant chr11-5249971-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 15035.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBG1	NM_000559.3	c.-167C>T		upstream_gene_variant		ENST00000330597.5	NP_000550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284931	ENST00000642908.1	c.316-1484C>T		intron_variant	Intron 2 of 2			ENSP00000495346.1
HBG1	ENST00000330597.5	c.-167C>T		upstream_gene_variant		1	NM_000559.3	ENSP00000327431.4

Frequencies

GnomAD3 genomes AF: 0.00000954 AC: 1 AN: 104850 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.0000417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000954 AC: 1 AN: 104850 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 49142

African (AFR) AF: 0.0000417 AC: 1 AN: 23970

American (AMR) AF: 0.00 AC: 0 AN: 9208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2692

East Asian (EAS) AF: 0.00 AC: 0 AN: 3676

South Asian (SAS) AF: 0.00 AC: 0 AN: 2670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52988

Other (OTH) AF: 0.00 AC: 0 AN: 1302

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary persistence of fetal hemoglobin Pathogenic:1

Mar 01, 1991

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		2.1
PromoterAI		-0.21	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs281860601; hg19: chr11-5271201;