chr16-72060377-T-G

Variant names:

• chr16-72060377-T-G
• rs192653057
• NM_005143.5:c.708T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005143.5(HP):​c.708T>G​(p.Val236Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,614,024 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: HP NM_005143.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170
• Publications: 0 publications found

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]

ENSG00000310525 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-72060377-T-G is Benign according to our data. Variant chr16-72060377-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 734198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.017 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005143.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	NM_005143.5	MANE Select	c.708T>G	p.Val236Val	synonymous	Exon 7 of 7	NP_005134.1	P00738-1
	HP	NM_001126102.3		c.531T>G	p.Val177Val	synonymous	Exon 5 of 5	NP_001119574.1	P00738-2
	HP	NM_001318138.2		c.531T>G	p.Val177Val	synonymous	Exon 5 of 5	NP_001305067.1	A0A0C4DGL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HP	ENST00000355906.10	TSL:1 MANE Select	c.708T>G	p.Val236Val	synonymous	Exon 7 of 7	ENSP00000348170.5	P00738-1
	HP	ENST00000398131.6	TSL:1	c.531T>G	p.Val177Val	synonymous	Exon 5 of 5	ENSP00000381199.2	P00738-2
	HP	ENST00000565574.5	TSL:1	c.531T>G	p.Val177Val	synonymous	Exon 5 of 5	ENSP00000454966.1	A0A0C4DGL8

Frequencies

GnomAD3 genomes AF: 0.000822 AC: 125 AN: 152122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000521 AC: 130 AN: 249390 AF XY: 0.000466

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00123

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000380

Gnomad OTH exome AF: 0.000660

GnomAD4 exome AF: 0.000395 AC: 577 AN: 1461784 Hom.: 3 Cov.: 31 AF XY: 0.000414 AC XY: 301 AN XY: 727196

African (AFR) AF: 0.00260 AC: 87 AN: 33474

American (AMR) AF: 0.00103 AC: 46 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39664

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86256

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000298 AC: 331 AN: 1111954

Other (OTH) AF: 0.000944 AC: 57 AN: 60390

GnomAD4 genome AF: 0.000854 AC: 130 AN: 152240 Hom.: 0 Cov.: 31 AF XY: 0.000927 AC XY: 69 AN XY: 74426

African (AFR) AF: 0.00188 AC: 78 AN: 41546

American (AMR) AF: 0.00164 AC: 25 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68018

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000402 Hom.: 0

Bravo AF: 0.00125

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.69
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism

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: rs192653057; hg19: chr16-72094276; COSMIC: COSV63326196; COSMIC: COSV63326196;