11-101127766-C-G

Variant names:

• chr11-101127766-C-G
• rs773981842
• NM_000926.4:c.1305G>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000926.4(PGR):​c.1305G>C​(p.Gly435Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,562,260 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: PGR NM_000926.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240
• Publications: 0 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]

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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-101127766-C-G is Benign according to our data. Variant chr11-101127766-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 713816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.024 with no splicing effect.
• BS2: High AC in GnomAd4 at 165 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1305G>C	p.Gly435Gly	synonymous	Exon 1 of 8	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.813G>C	p.Gly271Gly	synonymous	Exon 1 of 8	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.813G>C	p.Gly271Gly	synonymous	Exon 1 of 7	NP_001258090.1	P06401

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1305G>C	p.Gly435Gly	synonymous	Exon 1 of 8	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1305G>C	p.Gly435Gly	synonymous	Exon 1 of 7	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.1305G>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 165 AN: 151716 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000707 AC: 116 AN: 164052 AF XY: 0.000584

Gnomad AFR exome AF: 0.000336

Gnomad AMR exome AF: 0.000964

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000709

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.000658

GnomAD4 exome AF: 0.00149 AC: 2096 AN: 1410434 Hom.: 3 Cov.: 32 AF XY: 0.00139 AC XY: 970 AN XY: 698454

African (AFR) AF: 0.000212 AC: 7 AN: 32998

American (AMR) AF: 0.000833 AC: 32 AN: 38398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25314

East Asian (EAS) AF: 0.00 AC: 0 AN: 38064

South Asian (SAS) AF: 0.00 AC: 0 AN: 81392

European-Finnish (FIN) AF: 0.000744 AC: 26 AN: 34962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00177 AC: 1942 AN: 1094742

Other (OTH) AF: 0.00151 AC: 89 AN: 58956

GnomAD4 genome AF: 0.00109 AC: 165 AN: 151826 Hom.: 1 Cov.: 33 AF XY: 0.000890 AC XY: 66 AN XY: 74162

African (AFR) AF: 0.0000963 AC: 4 AN: 41536

American (AMR) AF: 0.000524 AC: 8 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 67754

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000359 Hom.: 0

Bravo AF: 0.00116

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		0.024
Mutation Taster		=100/0	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: rs773981842; hg19: chr11-100998497;