rs8603

chr19-43193077-G-Achr19-43193077-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002780.5(PSG4):c.*295C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 603,576 control chromosomes in the GnomAD database, including 141,090 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 0.69 (37339 hom., cov: 32)
  • Exomes 𝑓: 0.67 (103751 hom.)
• Consequence: PSG4 NM_002780.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

PSG4 (HGNC:9521): (pregnancy specific beta-1-glycoprotein 4) The protein encoded by this gene is a pregnancy-specific glycoprotein (PSG), one of several encoded by a cluster of similar genes on chromosome 19. This gene is a member of the carcinoembryonic antigen (CEA) gene family and may play a role in regulation of the innate immune system. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -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 = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSG4	NM_002780.5	c.*295C>T		3_prime_UTR_variant	6/6	ENST00000405312.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSG4	ENST00000405312.8	c.*295C>T		3_prime_UTR_variant	6/6	1	NM_002780.5	P1
PSG4	ENST00000244295.13	c.*295C>T		3_prime_UTR_variant	5/5	1
PSG4	ENST00000433626.6	c.*295C>T		3_prime_UTR_variant	5/5	2
PSG4	ENST00000490769.1	n.859C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 104472 AN: 151068 Hom.: 37287 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.622

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.667 AC: 301560 AN: 452392 Hom.: 103751 Cov.: 0 AF XY: 0.668 AC XY: 159889 AN XY: 239366

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.962

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome AF: 0.692 AC: 104585 AN: 151184 Hom.: 37339 Cov.: 32 AF XY: 0.691 AC XY: 51053 AN XY: 73898

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.679

Alfa AF: 0.670 Hom.: 4285

Bravo AF: 0.689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.6
Dann	Benign	0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs8603; hg19: chr19-43697229;