rs35134589

Variant names:

• chr11-625695-G-A
• rs35134589
• ENST00000674088.1:c.-266+326C>T

Variant summary

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

The ENST00000674088.1(CDHR5):​c.-266+326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,082 control chromosomes in the GnomAD database, including 4,371 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 0.23 (4371 hom., cov: 32)
• Consequence: CDHR5 ENST00000674088.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 7 publications found

Genes affected

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000674088.1	c.-266+326C>T		intron_variant	Intron 1 of 15			ENSP00000501074.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 151964 Hom.: 4370 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.0962

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.236

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35232 AN: 152082 Hom.: 4371 Cov.: 32 AF XY: 0.223 AC XY: 16603 AN XY: 74354

African (AFR) AF: 0.305 AC: 12660 AN: 41462

American (AMR) AF: 0.247 AC: 3772 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3466

East Asian (EAS) AF: 0.0250 AC: 129 AN: 5170

South Asian (SAS) AF: 0.0957 AC: 462 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10608

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15234 AN: 67944

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.240 Hom.: 588

Bravo AF: 0.243

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.76
PhyloP100		2.0
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35134589; hg19: chr11-625695;