ENST00000511044.1:n.2491G>T

Variant names:

• chr5-141863068-C-A
• rs14359
• ENST00000511044.1:n.2491G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000511044.1(PCDH1):​n.2491G>T 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 0.000000824 in 1,212,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: PCDH1 ENST00000511044.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 7 publications found

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511044.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH1	NM_032420.5	MANE Select	c.3099+164G>T		intron	N/A	NP_115796.2
	PCDH1	NM_001278613.2		c.*80G>T		3_prime_UTR	Exon 3 of 3	NP_001265542.1
	PCDH1	NM_002587.5		c.*80G>T		3_prime_UTR	Exon 3 of 3	NP_002578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH1	ENST00000511044.1	TSL:1	n.2491G>T		non_coding_transcript_exon	Exon 2 of 2
	PCDH1	ENST00000394536.4	TSL:1	c.*80G>T		3_prime_UTR	Exon 3 of 3	ENSP00000378043.3
	PCDH1	ENST00000287008.8	TSL:5 MANE Select	c.3099+164G>T		intron	N/A	ENSP00000287008.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.24e-7 AC: 1 AN: 1212886 Hom.: 0 Cov.: 32 AF XY: 0.00000173 AC XY: 1 AN XY: 579554

African (AFR) AF: 0.00 AC: 0 AN: 27584

American (AMR) AF: 0.00 AC: 0 AN: 15518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17258

East Asian (EAS) AF: 0.00 AC: 0 AN: 33160

South Asian (SAS) AF: 0.00 AC: 0 AN: 38878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 986946

Other (OTH) AF: 0.0000200 AC: 1 AN: 49976

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-0.030

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs14359; hg19: chr5-141242633;