rs6558295

Positions:

• chr8-144084619-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003801.4(GPAA1):​c.1010+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,607,866 control chromosomes in the GnomAD database, including 8,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2291 hom., cov: 33)
  • Exomes 𝑓: 0.083 (6434 hom.)
• Consequence: GPAA1 NM_003801.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.123

Genes affected

GPAA1 (HGNC:4446): (glycosylphosphatidylinositol anchor attachment 1) Posttranslational glycosylphosphatidylinositol (GPI) anchor attachment serves as a general mechanism for linking proteins to the cell surface membrane. The protein encoded by this gene presumably functions in GPI anchoring at the GPI transfer step. The mRNA transcript is ubiquitously expressed in both fetal and adult tissues. The anchor attachment protein 1 contains an N-terminal signal sequence, 1 cAMP- and cGMP-dependent protein kinase phosphorylation site, 1 leucine zipper pattern, 2 potential N-glycosylation sites, and 8 putative transmembrane domains. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-144084619-C-G is Benign according to our data. Variant chr8-144084619-C-G is described in ClinVar as [Benign]. Clinvar id is 1300876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAA1	NM_003801.4	c.1010+10C>G		intron_variant		ENST00000355091.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPAA1	ENST00000355091.9	c.1010+10C>G		intron_variant		1	NM_003801.4	P4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20977 AN: 152132 Hom.: 2283 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.0809 AC: 20034 AN: 247792 Hom.: 1380 AF XY: 0.0763 AC XY: 10251 AN XY: 134426

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.0537

Gnomad ASJ exome AF: 0.0766

Gnomad EAS exome AF: 0.00601

Gnomad SAS exome AF: 0.0387

Gnomad FIN exome AF: 0.0749

Gnomad NFE exome AF: 0.0818

Gnomad OTH exome AF: 0.0786

GnomAD4 exome AF: 0.0834 AC: 121364 AN: 1455616 Hom.: 6434 Cov.: 33 AF XY: 0.0813 AC XY: 58765 AN XY: 723232

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.0567

Gnomad4 ASJ exome AF: 0.0737

Gnomad4 EAS exome AF: 0.00415

Gnomad4 SAS exome AF: 0.0400

Gnomad4 FIN exome AF: 0.0746

Gnomad4 NFE exome AF: 0.0838

Gnomad4 OTH exome AF: 0.0883

GnomAD4 genome AF: 0.138 AC: 21020 AN: 152250 Hom.: 2291 Cov.: 33 AF XY: 0.134 AC XY: 9994 AN XY: 74440

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0876

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0420

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.123

Alfa AF: 0.103 Hom.: 237

Bravo AF: 0.148

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6558295; hg19: chr8-145139522; COSMIC: COSV60155456; COSMIC: COSV60155456;