16-83807608-G-T

Position:

• chr16-83807608-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000561599.2(CDH13-AS2):​n.227C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 160,976 control chromosomes in the GnomAD database, including 5,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4822 hom., cov: 32)
  • Exomes 𝑓: 0.20 (231 hom.)
• Consequence: CDH13-AS2 ENST00000561599.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.60

Genes affected

CDH13-AS2 (HGNC:56243): (CDH13 antisense RNA 2)

HSBP1 (HGNC:5203): (heat shock factor binding protein 1) The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-83807608-G-T is Benign according to our data. Variant chr16-83807608-G-T is described in ClinVar as [Benign]. Clinvar id is 1226958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13-AS2	ENST00000561599.2	n.227C>A		non_coding_transcript_exon_variant	1/5	4
HSBP1	ENST00000690173.1	n.98-427G>T		intron_variant, non_coding_transcript_variant
HSBP1	ENST00000693379.1	n.98-427G>T		intron_variant, non_coding_transcript_variant
HSBP1	ENST00000693758.1	n.98-427G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36815 AN: 151900 Hom.: 4822 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.200 AC: 1788 AN: 8958 Hom.: 231 Cov.: 0 AF XY: 0.198 AC XY: 978 AN XY: 4948

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0758

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.242 AC: 36825 AN: 152018 Hom.: 4822 Cov.: 32 AF XY: 0.243 AC XY: 18033 AN XY: 74296

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0979

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.235

Alfa AF: 0.240 Hom.: 1457

Bravo AF: 0.232

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11149602; hg19: chr16-83841213;