Genetic Variant NM_005716.4:c.852G>A (chr19-14478566-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005716.4(GIPC1):c.852G>A(p.Ala284Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4136 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30149 hom. )

Consequence

GIPC1
NM_005716.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001838

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.762

Publications

17 publications found

Variant links:

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]

GIPC1 Gene-Disease associations (from GenCC):

oculopharyngodistal myopathy 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
oculopharyngodistal myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GIPC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

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 rank	MANE	Protein	UniProt
GIPC1	NM_005716.4 link	c.852G>A	p.Ala284Ala	splice_region_variant, synonymous_variant	Exon 9 of 9	ENST00000393033.9	NP_005707.1	O14908-1A0A024R7I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPC1	ENST00000393033.9 link	c.852G>A	p.Ala284Ala	splice_region_variant, synonymous_variant	Exon 9 of 9	1	NM_005716.4	ENSP00000376753.3		O14908-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34616

AN:

151896

Hom.:

4121

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.214

AC:

53556

AN:

250246

AF XY:

0.210

show subpopulations

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 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.:

AF XY:

0.199

AC XY:

144521

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.261

AC:

8727

AN:

33478

American (AMR)

AF:

0.225

AC:

10073

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5531

AN:

26114

East Asian (EAS)

AF:

0.336

AC:

13355

AN:

39696

South Asian (SAS)

AF:

0.156

AC:

13489

AN:

86244

European-Finnish (FIN)

AF:

0.208

AC:

11079

AN:

53348

Middle Eastern (MID)

AF:

0.181

AC:

1046

AN:

5768

European-Non Finnish (NFE)

AF:

0.195

AC:

216772

AN:

1111542

Other (OTH)

AF:

0.212

AC:

12786

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

11501

23002

34503

46004

57505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.228

AC:

34675

AN:

152014

Hom.:

4136

Cov.:

AF XY:

0.229

AC XY:

17012

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.261

AC:

10822

AN:

41468

American (AMR)

AF:

0.255

AC:

3889

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

749

AN:

3468

East Asian (EAS)

AF:

0.321

AC:

1653

AN:

5144

South Asian (SAS)

AF:

0.168

AC:

810

AN:

4816

European-Finnish (FIN)

AF:

0.216

AC:

2281

AN:

10582

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13727

AN:

67946

Other (OTH)

AF:

0.249

AC:

526

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1372

2743

4115

5486

6858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.213

Hom.:

5604

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

(source)

DANN

Benign

0.90

PhyloP100

-0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=81/19

polymorphism (auto)

(source)

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

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NM_005716.4:c.852G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over