rs2000999

Variant names:

• chr16-72074194-G-A
• rs2000999
• NM_020995.4:c.92-90G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 166 publications found

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]

ENSG00000310525 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HPR	NM_020995.4	c.92-90G>A		intron_variant	Intron 2 of 4	ENST00000540303.7	NP_066275.3
HPR	NM_001384360.1	c.-269-90G>A		intron_variant	Intron 3 of 5		NP_001371289.1
HPR	XM_024450251.2	c.110-90G>A		intron_variant	Intron 2 of 4		XP_024306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPR	ENST00000540303.7	c.92-90G>A		intron_variant	Intron 2 of 4	1	NM_020995.4	ENSP00000441828.2
ENSG00000310525	ENST00000562153.6	n.284+14793C>T		intron_variant	Intron 3 of 5	4		ENSP00000454635.2

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

African (AFR) AF: 0.0594 AC: 1689 AN: 28418

American (AMR) AF: 0.172 AC: 7484 AN: 43462

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6269 AN: 24088

East Asian (EAS) AF: 0.333 AC: 12622 AN: 37870

South Asian (SAS) AF: 0.389 AC: 30850 AN: 79322

European-Finnish (FIN) AF: 0.192 AC: 10169 AN: 53046

Middle Eastern (MID) AF: 0.278 AC: 1260 AN: 4540

European-Non Finnish (NFE) AF: 0.195 AC: 159078 AN: 816094

Other (OTH) AF: 0.210 AC: 10414 AN: 49628

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

African (AFR) AF: 0.0649 AC: 2655 AN: 40924

American (AMR) AF: 0.181 AC: 2760 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1455 AN: 5130

South Asian (SAS) AF: 0.395 AC: 1902 AN: 4816

European-Finnish (FIN) AF: 0.188 AC: 1987 AN: 10588

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13555 AN: 67988

Other (OTH) AF: 0.198 AC: 416 AN: 2104

Alfa AF: 0.194 Hom.: 12016

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
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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