11-101091797-G-T

Variant names:

• chr11-101091797-G-T
• rs2020876
• NM_000926.4:c.1869C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000926.4(PGR):​c.1869C>A​(p.Arg623Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,607,146 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (103 hom.)
• Consequence: PGR NM_000926.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.19
• Publications: 6 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-101091797-G-T is Benign according to our data. Variant chr11-101091797-G-T is described in ClinVar as [Benign]. Clinvar id is 771450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00768 (1169/152262) while in subpopulation AMR AF = 0.0331 (506/15298). AF 95% confidence interval is 0.0307. There are 18 homozygotes in GnomAd4. There are 751 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1869C>A	p.Arg623Arg	synonymous_variant	Exon 3 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1869C>A	p.Arg623Arg	synonymous_variant	Exon 3 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1165 AN: 152146 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.0119 AC: 2989 AN: 251188 AF XY: 0.00993

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0500

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.00240

Gnomad FIN exome AF: 0.0360

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00898

GnomAD4 exome AF: 0.00369 AC: 5368 AN: 1454884 Hom.: 103 Cov.: 29 AF XY: 0.00341 AC XY: 2472 AN XY: 724368

African (AFR) AF: 0.000270 AC: 9 AN: 33342

American (AMR) AF: 0.0465 AC: 2080 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 533 AN: 26096

East Asian (EAS) AF: 0.00590 AC: 234 AN: 39654

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86132

European-Finnish (FIN) AF: 0.0333 AC: 1777 AN: 53364

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5752

European-Non Finnish (NFE) AF: 0.000398 AC: 440 AN: 1105686

Other (OTH) AF: 0.00441 AC: 265 AN: 60154

GnomAD4 genome AF: 0.00768 AC: 1169 AN: 152262 Hom.: 18 Cov.: 33 AF XY: 0.0101 AC XY: 751 AN XY: 74434

African (AFR) AF: 0.000626 AC: 26 AN: 41558

American (AMR) AF: 0.0331 AC: 506 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3472

East Asian (EAS) AF: 0.00599 AC: 31 AN: 5172

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.0420 AC: 445 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68020

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00322 Hom.: 4

Bravo AF: 0.00699

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.6
DANN	Benign	0.79
PhyloP100		2.2
Mutation Taster		=88/12	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: rs2020876; hg19: chr11-100962528;