chr11-101063100-G-T

Variant names:

• chr11-101063100-G-T
• rs1824128
• NM_000926.4:c.1907-348C>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.1907-348C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 225,018 control chromosomes in the GnomAD database, including 6,255 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 0.19 (3855 hom., cov: 32)
  • Exomes 𝑓: 0.21 (2400 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

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.1907-348C>A		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1415-348C>A		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1415-11532C>A		intron	N/A	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.1907-348C>A		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1907-11532C>A		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000533207.5	TSL:1	n.926C>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28244 AN: 151966 Hom.: 3849 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.210 AC: 15289 AN: 72934 Hom.: 2400 Cov.: 0 AF XY: 0.225 AC XY: 8750 AN XY: 38906

African (AFR) AF: 0.101 AC: 105 AN: 1042

American (AMR) AF: 0.298 AC: 1059 AN: 3556

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 266 AN: 1658

East Asian (EAS) AF: 0.764 AC: 2212 AN: 2896

South Asian (SAS) AF: 0.361 AC: 3736 AN: 10362

European-Finnish (FIN) AF: 0.165 AC: 592 AN: 3594

Middle Eastern (MID) AF: 0.129 AC: 32 AN: 248

European-Non Finnish (NFE) AF: 0.145 AC: 6619 AN: 45776

Other (OTH) AF: 0.176 AC: 668 AN: 3802

GnomAD4 genome AF: 0.186 AC: 28264 AN: 152084 Hom.: 3855 Cov.: 32 AF XY: 0.194 AC XY: 14410 AN XY: 74336

African (AFR) AF: 0.119 AC: 4921 AN: 41510

American (AMR) AF: 0.255 AC: 3893 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.760 AC: 3912 AN: 5150

South Asian (SAS) AF: 0.428 AC: 2062 AN: 4814

European-Finnish (FIN) AF: 0.173 AC: 1832 AN: 10582

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10546 AN: 67972

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.167 Hom.: 8059

Bravo AF: 0.188

Asia WGS AF: 0.581 AC: 2015 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.067
DANN	Benign	0.55
PhyloP100		-1.8
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: rs1824128; hg19: chr11-100933831;