11-101067937-C-T

Variant names:

• chr11-101067937-C-T
• rs666553
• NM_000926.4:c.1907-5185G>A

Variant summary

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

The NM_000926.4(PGR):​c.1907-5185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,854 control chromosomes in the GnomAD database, including 2,299 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 0.16 (2299 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 5 publications found

Genes affected

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1907-5185G>A		intron_variant	Intron 3 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1907-5185G>A		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24577 AN: 151738 Hom.: 2277 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.162 AC: 24648 AN: 151854 Hom.: 2299 Cov.: 32 AF XY: 0.160 AC XY: 11842 AN XY: 74202

African (AFR) AF: 0.252 AC: 10454 AN: 41440

American (AMR) AF: 0.159 AC: 2419 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 563 AN: 3464

East Asian (EAS) AF: 0.192 AC: 989 AN: 5152

South Asian (SAS) AF: 0.0644 AC: 310 AN: 4814

European-Finnish (FIN) AF: 0.103 AC: 1080 AN: 10518

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8376 AN: 67906

Other (OTH) AF: 0.154 AC: 325 AN: 2104

Alfa AF: 0.144 Hom.: 395

Bravo AF: 0.171

Asia WGS AF: 0.128 AC: 442 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.11
PhyloP100		-0.99
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: rs666553; hg19: chr11-100938668;