rs2844580

Positions:

• chr6-31365526-T-C

Variant summary

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

The ENST00000696690.1(ENSG00000293281):​n.1612+217A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,864 control chromosomes in the GnomAD database, including 7,934 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 0.31 (7934 hom., cov: 31)
• Consequence: ENST00000696690.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

(HGNC:):

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000696690.1	n.1612+217A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47372 AN: 151758 Hom.: 7932 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.312 AC: 47389 AN: 151864 Hom.: 7934 Cov.: 31 AF XY: 0.301 AC XY: 22320 AN XY: 74212

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.308

Alfa AF: 0.360 Hom.: 4363

Bravo AF: 0.311

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.5
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2844580; hg19: chr6-31333303;