rs2000999

chr16-72074194-G-A

Variant summary

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

The NM_020995.4(HPR):c.92-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,287,932 control chromosomes in the GnomAD database, including 31,177 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 0.17 (2784 hom., cov: 32)
  • Exomes 𝑓: 0.21 (28393 hom.)
• Consequence: HPR NM_020995.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

Genes affected

HPR (HGNC:5156): (haptoglobin-related protein) This gene encodes a haptoglobin-related protein that binds hemoglobin as efficiently as haptoglobin. Unlike haptoglobin, plasma concentration of this protein is unaffected in patients with sickle cell anemia and extensive intravascular hemolysis, suggesting a difference in binding between haptoglobin-hemoglobin and haptoglobin-related protein-hemoglobin complexes to CD163, the hemoglobin scavenger receptor. This protein may also be a clinically important predictor of recurrence of breast cancer. [provided by RefSeq, Oct 2011]

TXNL4B (HGNC:26041): (thioredoxin like 4B) Predicted to be involved in mRNA splicing, via spliceosome. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPR	NM_020995.4	c.92-90G>A		intron_variant		ENST00000540303.7
HPR	NM_001384360.1	c.-269-90G>A		intron_variant
HPR	XM_024450251.2	c.110-90G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPR	ENST00000540303.7	c.92-90G>A		intron_variant		1	NM_020995.4	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25742 AN: 151344 Hom.: 2786 Cov.: 32

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.211 AC: 239835 AN: 1136468 Hom.: 28393 AF XY: 0.219 AC XY: 127456 AN XY: 580740

Gnomad4 AFR exome AF: 0.0594

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.170 AC: 25736 AN: 151464 Hom.: 2784 Cov.: 32 AF XY: 0.174 AC XY: 12869 AN XY: 74030

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.198

Alfa AF: 0.200 Hom.: 5634

Bravo AF: 0.162

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.2
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs2000999; hg19: chr16-72108093; COSMIC: COSV57183415;