11-101034978-T-G

Variant names:

• chr11-101034978-T-G
• rs473409
• NM_000926.4:c.*4138A>C

Variant summary

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

The NM_000926.4(PGR):​c.*4138A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 193,660 control chromosomes in the GnomAD database, including 7,971 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 0.29 (6454 hom., cov: 33)
  • Exomes 𝑓: 0.27 (1517 hom.)
• Consequence: PGR NM_000926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 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.*4138A>C		3_prime_UTR	Exon 8 of 8	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.*4138A>C		3_prime_UTR	Exon 8 of 8	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.*4138A>C		3_prime_UTR	Exon 7 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.*4138A>C		3_prime_UTR	Exon 8 of 8	ENSP00000325120.5	P06401-1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43317 AN: 151952 Hom.: 6436 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.270 AC: 11238 AN: 41590 Hom.: 1517 Cov.: 0 AF XY: 0.271 AC XY: 5205 AN XY: 19206

African (AFR) AF: 0.357 AC: 614 AN: 1720

American (AMR) AF: 0.307 AC: 333 AN: 1084

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1011 AN: 2648

East Asian (EAS) AF: 0.234 AC: 1662 AN: 7090

South Asian (SAS) AF: 0.146 AC: 52 AN: 356

European-Finnish (FIN) AF: 0.0909 AC: 2 AN: 22

Middle Eastern (MID) AF: 0.262 AC: 68 AN: 260

European-Non Finnish (NFE) AF: 0.261 AC: 6515 AN: 25006

Other (OTH) AF: 0.288 AC: 981 AN: 3404

GnomAD4 genome AF: 0.285 AC: 43392 AN: 152070 Hom.: 6454 Cov.: 33 AF XY: 0.279 AC XY: 20758 AN XY: 74354

African (AFR) AF: 0.370 AC: 15347 AN: 41454

American (AMR) AF: 0.298 AC: 4550 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3466

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5166

South Asian (SAS) AF: 0.133 AC: 644 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2308 AN: 10590

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17086 AN: 67972

Other (OTH) AF: 0.306 AC: 647 AN: 2112

Alfa AF: 0.272 Hom.: 742

Bravo AF: 0.298

Asia WGS AF: 0.199 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		0.044
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: rs473409; hg19: chr11-100905709;