ENST00000696559.1:c.-204+1691G>A

Variant names:

• chr6-31364052-C-T
• rs2523554
• ENST00000696559.1:c.-204+1691G>A

Variant summary

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

The ENST00000696559.1(HLA-B):​c.-204+1691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,614 control chromosomes in the GnomAD database, including 38,017 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 0.70 (38017 hom., cov: 30)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

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]

DHFRP2 (HGNC:2863): (dihydrofolate reductase pseudogene 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHFRP2		n.31364052C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696559.1	c.-204+1691G>A		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-204+1691G>A		intron_variant	Intron 1 of 9			ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-299-1038G>A		intron_variant	Intron 2 of 11			ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106273 AN: 151500 Hom.: 37968 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.702 AC: 106379 AN: 151614 Hom.: 38017 Cov.: 30 AF XY: 0.710 AC XY: 52543 AN XY: 74026

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.769

Alfa AF: 0.651 Hom.: 61262

Bravo AF: 0.716

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.5
DANN	Benign	0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523554; hg19: chr6-31331829;