rs7214635

Positions:

• chr17-4697725-G-A
• chr17-4697725-G-C
• chr17-4697725-G-T

Variant summary

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

The NM_014389.3(PELP1):​c.249+6138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,092 control chromosomes in the GnomAD database, including 48,570 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 0.80 (48570 hom., cov: 30)
• Consequence: PELP1 NM_014389.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PELP1	NM_014389.3	c.249+6138C>T		intron_variant		ENST00000572293.7
PELP1	NM_001278241.2	c.-275+6138C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PELP1	ENST00000572293.7	c.249+6138C>T		intron_variant		1	NM_014389.3	A2

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121213 AN: 151974 Hom.: 48520 Cov.: 30

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.798 AC: 121319 AN: 152092 Hom.: 48570 Cov.: 30 AF XY: 0.803 AC XY: 59677 AN XY: 74346

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.797

Alfa AF: 0.766 Hom.: 16545

Bravo AF: 0.802

Asia WGS AF: 0.924 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.1
DANN	Benign	0.96

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: rs7214635; hg19: chr17-4601020;