rs8603

Variant names:

• chr19-43193077-G-A
• rs8603
• NM_002780.5:c.*295C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43193077-G-A
• chr19-43193077-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

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 = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002780.5. 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
	PSG4	NM_002780.5	MANE Select	c.*295C>T		3_prime_UTR	Exon 6 of 6	NP_002771.2
	PSG4	NM_001276495.2		c.*295C>T		3_prime_UTR	Exon 5 of 5	NP_001263424.1	Q00888-3
	PSG4	NM_213633.3		c.*295C>T		3_prime_UTR	Exon 5 of 5	NP_998798.1	Q00888-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSG4	ENST00000405312.8	TSL:1 MANE Select	c.*295C>T		3_prime_UTR	Exon 6 of 6	ENSP00000384770.3	Q00888-1
	PSG4	ENST00000244295.13	TSL:1	c.*295C>T		3_prime_UTR	Exon 5 of 5	ENSP00000244295.8	Q00888-2
	PSG4	ENST00000433626.6	TSL:2	c.*295C>T		3_prime_UTR	Exon 5 of 5	ENSP00000387864.2	Q00888-3

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

African (AFR) AF: 0.794 AC: 10001 AN: 12602

American (AMR) AF: 0.603 AC: 12325 AN: 20442

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 8490 AN: 13678

East Asian (EAS) AF: 0.962 AC: 30103 AN: 31302

South Asian (SAS) AF: 0.707 AC: 32437 AN: 45848

European-Finnish (FIN) AF: 0.650 AC: 19454 AN: 29924

Middle Eastern (MID) AF: 0.634 AC: 1256 AN: 1982

European-Non Finnish (NFE) AF: 0.630 AC: 170336 AN: 270584

Other (OTH) AF: 0.659 AC: 17158 AN: 26030

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

African (AFR) AF: 0.797 AC: 32756 AN: 41076

American (AMR) AF: 0.640 AC: 9689 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2190 AN: 3412

East Asian (EAS) AF: 0.931 AC: 4810 AN: 5164

South Asian (SAS) AF: 0.719 AC: 3445 AN: 4794

European-Finnish (FIN) AF: 0.643 AC: 6779 AN: 10542

Middle Eastern (MID) AF: 0.614 AC: 178 AN: 290

European-Non Finnish (NFE) AF: 0.631 AC: 42787 AN: 67774

Other (OTH) AF: 0.679 AC: 1421 AN: 2092

Alfa AF: 0.670 Hom.: 4285

Bravo AF: 0.689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.14
PhyloP100		-1.0
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: rs8603; hg19: chr19-43697229;