16-64947363-GT-GTTT

Variant names:

• chr16-64947363-G-GTT
• rs34181449
• NM_001797.4:c.*238_*239dupAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001797.4(CDH11):​c.*238_*239dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 1,147,582 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: CDH11 NM_001797.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

Genes affected

CDH11 (HGNC:1750): (cadherin 11) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000056 (56/999532) while in subpopulation SAS AF= 0.000282 (9/31968). AF 95% confidence interval is 0.000147. There are 0 homozygotes in gnomad4_exome. There are 34 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH11	NM_001797.4	c.*238_*239dupAA		3_prime_UTR_variant	Exon 13 of 13	ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.*726_*727dupAA		3_prime_UTR_variant	Exon 14 of 14		NP_001295321.1
CDH11	NM_001330576.2	c.*238_*239dupAA		3_prime_UTR_variant	Exon 12 of 12		NP_001317505.1
CDH11	XM_047433486.1	c.*238_*239dupAA		3_prime_UTR_variant	Exon 12 of 12		XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603	c.*238_*239dupAA		3_prime_UTR_variant	Exon 13 of 13	1	NM_001797.4	ENSP00000268603.4
CDH11	ENST00000394156	c.*726_*727dupAA		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000377711.3
CDH11	ENST00000566827.5	c.*238_*239dupAA		downstream_gene_variant		2		ENSP00000457812.1

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000560 AC: 56 AN: 999532 Hom.: 0 Cov.: 27 AF XY: 0.0000717 AC XY: 34 AN XY: 474484

Gnomad4 AFR exome AF: 0.0000442

Gnomad4 AMR exome AF: 0.000200

Gnomad4 ASJ exome AF: 0.0000752

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.000282

Gnomad4 FIN exome AF: 0.000194

Gnomad4 NFE exome AF: 0.0000429

Gnomad4 OTH exome AF: 0.0000250

GnomAD4 genome AF: 0.00000675 AC: 1 AN: 148050 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 72098

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000150

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34181449; hg19: chr16-64981266;