rs1134590

Variant names:

• chr14-105721893-C-T
• rs1134590
• unassigned_transcript_2474:c.552G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000000000(IGHEP1):​c.552G>A​(p.Glu184Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 768,000 control chromosomes in the GnomAD database, including 198,530 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 0.74 (42417 hom., cov: 30)
  • Exomes 𝑓: 0.70 (156113 hom.)
• Consequence: IGHEP1 ENST00000000000 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 5 publications found

Genes affected

IGHEP1 (HGNC:5523): (immunoglobulin heavy constant epsilon P1 (pseudogene))

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521393.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHEP1	ENST00000521393.1	TSL:6	n.552G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.741 AC: 111825 AN: 150944 Hom.: 42380 Cov.: 30

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.781

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.734

GnomAD2 exomes AF: 0.683 AC: 160797 AN: 235534 AF XY: 0.693

Gnomad AFR exome AF: 0.859

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.783

Gnomad EAS exome AF: 0.656

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.749

Gnomad OTH exome AF: 0.699

GnomAD4 exome AF: 0.703 AC: 433826 AN: 616940 Hom.: 156113 Cov.: 0 AF XY: 0.708 AC XY: 237790 AN XY: 336064

African (AFR) AF: 0.853 AC: 14985 AN: 17576

American (AMR) AF: 0.447 AC: 17897 AN: 40012

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 16021 AN: 20802

East Asian (EAS) AF: 0.501 AC: 17515 AN: 34936

South Asian (SAS) AF: 0.667 AC: 45559 AN: 68304

European-Finnish (FIN) AF: 0.678 AC: 35383 AN: 52164

Middle Eastern (MID) AF: 0.776 AC: 3090 AN: 3980

European-Non Finnish (NFE) AF: 0.750 AC: 259737 AN: 346518

Other (OTH) AF: 0.724 AC: 23639 AN: 32648

GnomAD4 genome AF: 0.741 AC: 111897 AN: 151060 Hom.: 42417 Cov.: 30 AF XY: 0.728 AC XY: 53674 AN XY: 73686

African (AFR) AF: 0.850 AC: 35046 AN: 41234

American (AMR) AF: 0.541 AC: 8180 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2642 AN: 3468

East Asian (EAS) AF: 0.628 AC: 3089 AN: 4920

South Asian (SAS) AF: 0.622 AC: 2943 AN: 4732

European-Finnish (FIN) AF: 0.660 AC: 6946 AN: 10530

Middle Eastern (MID) AF: 0.775 AC: 220 AN: 284

European-Non Finnish (NFE) AF: 0.747 AC: 50600 AN: 67780

Other (OTH) AF: 0.734 AC: 1535 AN: 2090

Alfa AF: 0.753 Hom.: 8051

Bravo AF: 0.733

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.3
DANN	Benign	0.71
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs1134590; hg19: chr14-106188230;