16-83807556-G-T

Variant names:

• chr16-83807556-G-T
• rs41103
• ENST00000561599.2:n.279C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561599.2(CDH13-AS2):​n.279C>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 0.342 in 154,436 control chromosomes in the GnomAD database, including 9,326 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 0.34 (9163 hom., cov: 32)
  • Exomes 𝑓: 0.33 (163 hom.)
• Consequence: CDH13-AS2 ENST00000561599.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561599.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13-AS2	ENST00000561599.2	TSL:4	n.279C>A		non_coding_transcript_exon	Exon 1 of 5
	CDH13-AS2	ENST00000743018.1		n.279C>A		non_coding_transcript_exon	Exon 1 of 4
	CDH13-AS2	ENST00000743019.1		n.275C>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51932 AN: 151900 Hom.: 9156 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.329 AC: 796 AN: 2418 Hom.: 163 Cov.: 0 AF XY: 0.333 AC XY: 485 AN XY: 1458

African (AFR) AF: 0.156 AC: 5 AN: 32

American (AMR) AF: 0.191 AC: 50 AN: 262

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 12 AN: 32

East Asian (EAS) AF: 0.192 AC: 5 AN: 26

South Asian (SAS) AF: 0.294 AC: 182 AN: 618

European-Finnish (FIN) AF: 0.273 AC: 12 AN: 44

Middle Eastern (MID) AF: 0.500 AC: 6 AN: 12

European-Non Finnish (NFE) AF: 0.385 AC: 488 AN: 1266

Other (OTH) AF: 0.286 AC: 36 AN: 126

GnomAD4 genome AF: 0.342 AC: 51970 AN: 152018 Hom.: 9163 Cov.: 32 AF XY: 0.334 AC XY: 24793 AN XY: 74282

African (AFR) AF: 0.398 AC: 16501 AN: 41434

American (AMR) AF: 0.230 AC: 3526 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3464

East Asian (EAS) AF: 0.167 AC: 864 AN: 5162

South Asian (SAS) AF: 0.293 AC: 1417 AN: 4830

European-Finnish (FIN) AF: 0.297 AC: 3137 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24005 AN: 67954

Other (OTH) AF: 0.311 AC: 657 AN: 2110

Alfa AF: 0.336 Hom.: 15676

Bravo AF: 0.339

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.60
PhyloP100		-0.041
PromoterAI		-0.00030	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41103;

hg19: chr16-83841161;