chr16-72074293-T-G

Position:

• chr16-72074293-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001384360.1(HPR):​c.-260T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 1,613,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (2 hom.)
• Consequence: HPR NM_001384360.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021121502).
• BP6: Variant 16-72074293-T-G is Benign according to our data. Variant chr16-72074293-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2346741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPR	NM_020995.4	c.101T>G	p.Phe34Cys	missense_variant	3/5	ENST00000540303.7	NP_066275.3
HPR	NM_001384360.1	c.-260T>G		5_prime_UTR_premature_start_codon_gain_variant	4/6		NP_001371289.1
HPR	XM_024450251.2	c.119T>G	p.Phe40Cys	missense_variant	3/5		XP_024306019.1
HPR	NM_001384360.1	c.-260T>G		5_prime_UTR_variant	4/6		NP_001371289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPR	ENST00000540303.7	c.101T>G	p.Phe34Cys	missense_variant	3/5	1	NM_020995.4	ENSP00000441828.2
TXNL4B	ENST00000562153.5	c.284+14694A>C		intron_variant		4		ENSP00000454635.2

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000260 AC: 65 AN: 249530 Hom.: 1 AF XY: 0.000295 AC XY: 40 AN XY: 135382

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.000223

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000311 AC: 454 AN: 1461618 Hom.: 2 Cov.: 32 AF XY: 0.000312 AC XY: 227 AN XY: 727134

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000696

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000298

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74300

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000309 Hom.: 0

Bravo AF: 0.000223

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000265 AC: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.1
DANN	Benign	0.25
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.079	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.021	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	-1.8	N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	5.9	N;.
REVEL	Benign	0.24
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.24
MVP		0.45
MPC		0.13
ClinPred		0.027	T
GERP RS		-1.4
Varity_R		0.037
gMVP		0.56

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: rs200255876; hg19: chr16-72108192; COSMIC: COSV57183127;