chr11-101129483-C-T

Variant names:

• chr11-101129483-C-T
• rs10895068
• ENST00000632820.1:n.407C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000632820.1(PGR-AS1):​n.407C>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 0.037 in 238,568 control chromosomes in the GnomAD database, including 240 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 0.036 (142 hom., cov: 31)
  • Exomes 𝑓: 0.039 (98 hom.)
• Consequence: PGR-AS1 ENST00000632820.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 104 publications found

Genes affected

PGR-AS1 (HGNC:52650): (PGR antisense RNA 1)

PGR (HGNC:8910): (progesterone receptor) This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000632820.1. 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
	PGR	NM_000926.4	MANE Select	c.-413G>A		5_prime_UTR	Exon 1 of 8	NP_000917.3
	PGR-AS1	NR_073144.1		n.407C>T		non_coding_transcript_exon	Exon 1 of 5
	PGR	NM_001271162.2		c.-201G>A		5_prime_UTR	Exon 1 of 8	NP_001258091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR-AS1	ENST00000632820.1	TSL:1	n.407C>T		non_coding_transcript_exon	Exon 1 of 7
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.-413G>A		5_prime_UTR	Exon 1 of 8	ENSP00000325120.5
	PGR	ENST00000619228.2	TSL:5	c.-413G>A		5_prime_UTR	Exon 1 of 5	ENSP00000482698.1

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5445 AN: 152078 Hom.: 142 Cov.: 31

Gnomad AFR AF: 0.00987

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0392 AC: 3389 AN: 86372 Hom.: 98 Cov.: 0 AF XY: 0.0383 AC XY: 1564 AN XY: 40830

African (AFR) AF: 0.0117 AC: 43 AN: 3684

American (AMR) AF: 0.0238 AC: 87 AN: 3652

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 166 AN: 4712

East Asian (EAS) AF: 0.000289 AC: 3 AN: 10382

South Asian (SAS) AF: 0.00514 AC: 7 AN: 1362

European-Finnish (FIN) AF: 0.0376 AC: 41 AN: 1090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 430

European-Non Finnish (NFE) AF: 0.0510 AC: 2779 AN: 54484

Other (OTH) AF: 0.0400 AC: 263 AN: 6576

GnomAD4 genome AF: 0.0358 AC: 5445 AN: 152196 Hom.: 142 Cov.: 31 AF XY: 0.0331 AC XY: 2460 AN XY: 74420

African (AFR) AF: 0.00984 AC: 409 AN: 41558

American (AMR) AF: 0.0321 AC: 491 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3472

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4826

European-Finnish (FIN) AF: 0.0375 AC: 397 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3866 AN: 67980

Other (OTH) AF: 0.0261 AC: 55 AN: 2110

Alfa AF: 0.0439 Hom.: 92

Bravo AF: 0.0335

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.3
DANN	Benign	0.91
PhyloP100		0.30
PromoterAI		-0.0036	Neutral
Mutation Taster		=300/0	polymorphism

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: rs10895068; hg19: chr11-101000214;