rs7245708

Positions:

• chr19-45692498-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000677024.1(QPCTL):​c.-206A>C variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 463,776 control chromosomes in the GnomAD database, including 380 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 0.028 (100 hom., cov: 33)
  • Exomes 𝑓: 0.036 (280 hom.)
• Consequence: QPCTL ENST00000677024.1 5_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934

Genes affected

QPCTL (HGNC:25952): (glutaminyl-peptide cyclotransferase like) Enables glutaminyl-peptide cyclotransferase activity and zinc ion binding activity. Acts upstream of or within peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

SNRPD2 (HGNC:11159): (small nuclear ribonucleoprotein D2 polypeptide) The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0281 (4286/152354) while in subpopulation NFE AF= 0.0456 (3102/68036). AF 95% confidence interval is 0.0443. There are 100 homozygotes in gnomad4. There are 2058 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QPCTL	ENST00000677024.1	c.-206A>C		5_prime_UTR_variant, NMD_transcript_variant	1/6			ENSP00000503301
QPCTL	ENST00000677542.1	c.-206A>C		5_prime_UTR_variant, NMD_transcript_variant	1/7			ENSP00000504457
QPCTL	ENST00000678102.1	c.-206A>C		5_prime_UTR_variant, NMD_transcript_variant	1/7			ENSP00000504441
SNRPD2	ENST00000587579.1	n.54+18T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4287 AN: 152236 Hom.: 100 Cov.: 33

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0356 AC: 11081 AN: 311422 Hom.: 280 Cov.: 5 AF XY: 0.0344 AC XY: 5507 AN XY: 160088

Gnomad4 AFR exome AF: 0.00868

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0105

Gnomad4 EAS exome AF: 0.0000401

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.0456

Gnomad4 OTH exome AF: 0.0326

GnomAD4 genome AF: 0.0281 AC: 4286 AN: 152354 Hom.: 100 Cov.: 33 AF XY: 0.0276 AC XY: 2058 AN XY: 74508

Gnomad4 AFR AF: 0.00822

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.0456

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0405 Hom.: 64

Bravo AF: 0.0252

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.67

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: rs7245708; hg19: chr19-46195756;