7-106004646-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_152750.5(CDHR3):c.1011C>T(p.Asp337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,613,982 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (6 hom.)
• Consequence: CDHR3 NM_152750.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.894

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 7-106004646-C-T is Benign according to our data. Variant chr7-106004646-C-T is described in ClinVar as [Benign]. Clinvar id is 782849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.894 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5	c.1011C>T	p.Asp337=	synonymous_variant	8/19	ENST00000317716.14
CDHR3	NM_001301161.2	c.747C>T	p.Asp249=	synonymous_variant	7/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14	c.1011C>T	p.Asp337=	synonymous_variant	8/19	1	NM_152750.5	P1

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 247 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00170 AC: 424 AN: 249224 Hom.: 1 AF XY: 0.00166 AC XY: 225 AN XY: 135204

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00260

Gnomad NFE exome AF: 0.00293

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00241 AC: 3516 AN: 1461690 Hom.: 6 Cov.: 31 AF XY: 0.00239 AC XY: 1736 AN XY: 727124

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000738

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00247

Gnomad4 NFE exome AF: 0.00291

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.00191 AC XY: 142 AN XY: 74458

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00248 Hom.: 0

Bravo AF: 0.00141

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00231

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	12
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7783527; hg19: chr7-105645092;