17-4679728-A-G

Variant names:

• chr17-4679728-A-G
• rs4790674
• NM_014389.3:c.642+2774T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014389.3. 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
	PELP1	NM_014389.3	MANE Select	c.642+2774T>C		intron	N/A	NP_055204.4
	PELP1	NM_001278241.2		c.201+2774T>C		intron	N/A	NP_001265170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELP1	ENST00000572293.7	TSL:1 MANE Select	c.642+2774T>C		intron	N/A	ENSP00000460300.2
	PELP1	ENST00000301396.8	TSL:1	c.792+2774T>C		intron	N/A	ENSP00000301396.5
	PELP1	ENST00000574876.5	TSL:1	c.642+2774T>C		intron	N/A	ENSP00000461625.1

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

African (AFR) AF: 0.533 AC: 22106 AN: 41488

American (AMR) AF: 0.744 AC: 11368 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2527 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5180 AN: 5192

South Asian (SAS) AF: 0.873 AC: 4206 AN: 4820

European-Finnish (FIN) AF: 0.796 AC: 8436 AN: 10592

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48768 AN: 67960

Other (OTH) AF: 0.685 AC: 1449 AN: 2114

Alfa AF: 0.696 Hom.: 4824

Bravo AF: 0.678

Asia WGS AF: 0.895 AC: 3111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.57
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs4790674; hg19: chr17-4583023;