chr19-14478566-C-T

Position:

• chr19-14478566-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The ENST00000393033.9(GIPC1):​c.852G>A​(p.Ala284=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,290 control chromosomes in the GnomAD database, including 34,285 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4136 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30149 hom.)
• Consequence: GIPC1 ENST00000393033.9 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001838
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

Genes affected

GIPC1 (HGNC:1226): (GIPC PDZ domain containing family member 1) GIPC1 is a scaffolding protein that regulates cell surface receptor expression and trafficking (Lee et al., 2008 [PubMed 18775991]).[supplied by OMIM, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 19-14478566-C-T is Benign according to our data. Variant chr19-14478566-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIPC1	NM_005716.4	c.852G>A	p.Ala284=	splice_region_variant, synonymous_variant	9/9	ENST00000393033.9	NP_005707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPC1	ENST00000393033.9	c.852G>A	p.Ala284=	splice_region_variant, synonymous_variant	9/9	1	NM_005716.4	ENSP00000376753	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34616 AN: 151896 Hom.: 4121 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.214 AC: 53556 AN: 250246 Hom.: 5960 AF XY: 0.210 AC XY: 28399 AN XY: 135392

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.157

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.200 AC: 292858 AN: 1461276 Hom.: 30149 Cov.: 34 AF XY: 0.199 AC XY: 144521 AN XY: 726956

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.228 AC: 34675 AN: 152014 Hom.: 4136 Cov.: 32 AF XY: 0.229 AC XY: 17012 AN XY: 74320

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.249

Alfa AF: 0.208 Hom.: 3406

Bravo AF: 0.234

Asia WGS AF: 0.257 AC: 891 AN: 3478

EpiCase AF: 0.204

EpiControl AF: 0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.030
SpliceAI score (max)		0.93		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.93		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1127307; hg19: chr19-14589378; COSMIC: COSV52876126; COSMIC: COSV52876126;