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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHEP1	unassigned_transcript_2474	c.552G>A	p.Glu184Glu	synonymous_variant	Exon 2 of 2
IGH		n.105721893C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHEP1	ENST00000521393.1	n.552G>A		non_coding_transcript_exon_variant	Exon 2 of 2	6

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 v4.3

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;