20-5561446-T-C

Variant names:

• chr20-5561446-T-C
• rs2273372
• NM_019593.5:c.1395+19A>G

Variant summary

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

The NM_019593.5(GPCPD1):​c.1395+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,388,054 control chromosomes in the GnomAD database, including 33,176 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 0.25 (5069 hom., cov: 33)
  • Exomes 𝑓: 0.21 (28107 hom.)
• Consequence: GPCPD1 NM_019593.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 8 publications found

Genes affected

GPCPD1 (HGNC:26957): (glycerophosphocholine phosphodiesterase 1) Predicted to enable glycerophosphocholine phosphodiesterase activity. Predicted to be involved in glycerophospholipid catabolic process. Predicted to act upstream of or within skeletal muscle tissue development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019593.5. 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
	GPCPD1	NM_019593.5	MANE Select	c.1395+19A>G		intron	N/A	NP_062539.1	Q9NPB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPCPD1	ENST00000379019.7	TSL:1 MANE Select	c.1395+19A>G		intron	N/A	ENSP00000368305.4	Q9NPB8
	GPCPD1	ENST00000718343.1		c.1395+19A>G		intron	N/A	ENSP00000520780.1	Q9NPB8
	GPCPD1	ENST00000873924.1		c.1395+19A>G		intron	N/A	ENSP00000543983.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37424 AN: 152074 Hom.: 5052 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.223 AC: 55385 AN: 247996 AF XY: 0.222

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.438

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.207 AC: 255699 AN: 1235860 Hom.: 28107 Cov.: 17 AF XY: 0.207 AC XY: 129458 AN XY: 625818

African (AFR) AF: 0.329 AC: 9467 AN: 28800

American (AMR) AF: 0.153 AC: 6714 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 4885 AN: 24708

East Asian (EAS) AF: 0.382 AC: 14618 AN: 38276

South Asian (SAS) AF: 0.197 AC: 15898 AN: 80798

European-Finnish (FIN) AF: 0.195 AC: 10303 AN: 52722

Middle Eastern (MID) AF: 0.235 AC: 1256 AN: 5336

European-Non Finnish (NFE) AF: 0.199 AC: 181056 AN: 908790

Other (OTH) AF: 0.219 AC: 11502 AN: 52590

GnomAD4 genome AF: 0.246 AC: 37488 AN: 152194 Hom.: 5069 Cov.: 33 AF XY: 0.243 AC XY: 18100 AN XY: 74412

African (AFR) AF: 0.335 AC: 13890 AN: 41496

American (AMR) AF: 0.194 AC: 2974 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 668 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2210 AN: 5178

South Asian (SAS) AF: 0.207 AC: 1001 AN: 4826

European-Finnish (FIN) AF: 0.181 AC: 1922 AN: 10600

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14082 AN: 68008

Other (OTH) AF: 0.239 AC: 505 AN: 2110

Alfa AF: 0.223 Hom.: 3364

Bravo AF: 0.254

Asia WGS AF: 0.326 AC: 1131 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.44
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2273372; hg19: chr20-5542092; COSMIC: COSV66830888;