rs3898917

Variant names:

• chr11-5307131-C-A
• rs3898917
• ENST00000292896.3:c.-266-36975G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5307131-C-A
• chr11-5307131-C-G
• chr11-5307131-C-T

Variant summary

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

The ENST00000292896.3(HBE1):​c.-266-36975G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,020 control chromosomes in the GnomAD database, including 30,812 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 0.61 (30812 hom., cov: 32)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 5 publications found

Genes affected

HBE1 (HGNC:4830): (hemoglobin subunit epsilon 1) The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains (an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form the embryonic Hb Gower II. Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon - G-gamma - A-gamma - delta - beta-3' [provided by RefSeq, Jul 2008]

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]

OR51B5 (HGNC:19599): (olfactory receptor family 51 subfamily B member 5) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000292896.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBE1	ENST00000292896.3	TSL:1	c.-266-36975G>T		intron	N/A	ENSP00000292896.2	P02100
	HBE1	ENST00000380237.5	TSL:1	c.-309-25180G>T		intron	N/A	ENSP00000369586.1	P02100
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*866+38642G>T		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91965 AN: 151898 Hom.: 30803 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.605 AC: 92005 AN: 152020 Hom.: 30812 Cov.: 32 AF XY: 0.601 AC XY: 44683 AN XY: 74304

African (AFR) AF: 0.319 AC: 13242 AN: 41448

American (AMR) AF: 0.657 AC: 10044 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2432 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1621 AN: 5174

South Asian (SAS) AF: 0.620 AC: 2993 AN: 4824

European-Finnish (FIN) AF: 0.734 AC: 7747 AN: 10560

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51828 AN: 67946

Other (OTH) AF: 0.611 AC: 1289 AN: 2110

Alfa AF: 0.713 Hom.: 113309

Bravo AF: 0.582

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		0.068
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: rs3898917; hg19: chr11-5328361;