16-72060233-T-G

Position:

• chr16-72060233-T-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005143.5(HP):​c.564T>G​(p.Gly188Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 152,266 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 0.0033 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: HP NM_005143.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.911

Genes affected

HP (HGNC:5141): (haptoglobin) This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

TXNL4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 16-72060233-T-G is Benign according to our data. Variant chr16-72060233-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 782963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.911 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HP	NM_005143.5	c.564T>G	p.Gly188Gly	synonymous_variant	7/7	ENST00000355906.10	NP_005134.1
HP	NM_001126102.3	c.387T>G	p.Gly129Gly	synonymous_variant	5/5		NP_001119574.1
HP	NM_001318138.2	c.387T>G	p.Gly129Gly	synonymous_variant	5/5		NP_001305067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HP	ENST00000355906.10	c.564T>G	p.Gly188Gly	synonymous_variant	7/7	1	NM_005143.5	ENSP00000348170.5
TXNL4B	ENST00000562153.5	c.285-15876A>C		intron_variant		4		ENSP00000454635.2

Frequencies

GnomAD3 genomes AF: 0.00327 AC: 497 AN: 152146 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00144 AC: 359 AN: 248890 Hom.: 5 AF XY: 0.00143 AC XY: 193 AN XY: 135022

Gnomad AFR exome AF: 0.00285

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00184

Gnomad SAS exome AF: 0.00161

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00149

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00156 AC: 2269 AN: 1458452 Hom.: 23 Cov.: 31 AF XY: 0.00159 AC XY: 1152 AN XY: 725608

Gnomad4 AFR exome AF: 0.00282

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00232

Gnomad4 SAS exome AF: 0.00253

Gnomad4 FIN exome AF: 0.000506

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00327 AC: 498 AN: 152266 Hom.: 2 Cov.: 31 AF XY: 0.00339 AC XY: 252 AN XY: 74444

Gnomad4 AFR AF: 0.00501

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00243 Hom.: 1

Bravo AF: 0.00329

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 13, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	HP: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.58

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: rs588482; hg19: chr16-72094132; COSMIC: COSV63325669; COSMIC: COSV63325669;