17-4679728-A-G

Position:

• chr17-4679728-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014389.3(PELP1):​c.642+2774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,120 control chromosomes in the GnomAD database, including 36,989 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 0.69 (36989 hom., cov: 32)
• Consequence: PELP1 NM_014389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

Genes affected

PELP1 (HGNC:30134): (proline, glutamate and leucine rich protein 1) This gene encodes a transcription factor which coactivates transcription of estrogen receptor responsive genes and corepresses genes activated by other hormone receptors or sequence-specific transcription factors. Expression of this gene is regulated by both members of the estrogen receptor family. This gene may be involved in the progression of several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ENSG00000235085 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELP1	NM_014389.3	c.642+2774T>C		intron_variant		ENST00000572293.7	NP_055204.4
PELP1	NM_001278241.2	c.201+2774T>C		intron_variant			NP_001265170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELP1	ENST00000572293.7	c.642+2774T>C		intron_variant		1	NM_014389.3	ENSP00000460300.2

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104656 AN: 152002 Hom.: 36957 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.688 AC: 104729 AN: 152120 Hom.: 36989 Cov.: 32 AF XY: 0.697 AC XY: 51816 AN XY: 74370

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.685

Alfa AF: 0.702 Hom.: 4698

Bravo AF: 0.678

Asia WGS AF: 0.895 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs4790674; hg19: chr17-4583023;