rs4245660

chr1-78075049-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017655.6(GIPC2):c.241-5626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,994 control chromosomes in the GnomAD database, including 21,486 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 0.52 (21486 hom., cov: 32)
• Consequence: GIPC2 NM_017655.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

Genes affected

GIPC2 (HGNC:18177): (GIPC PDZ domain containing family member 2) Enables identical protein binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPC2	NM_017655.6	c.241-5626C>T		intron_variant		ENST00000370759.4
GIPC2	NM_001304725.2	c.19-5626C>T		intron_variant
GIPC2	XM_047423230.1	c.391-5626C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPC2	ENST00000370759.4	c.241-5626C>T		intron_variant		1	NM_017655.6	P1
GIPC2	ENST00000476882.1	n.79-5626C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78541 AN: 151876 Hom.: 21474 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.517 AC: 78576 AN: 151994 Hom.: 21486 Cov.: 32 AF XY: 0.521 AC XY: 38694 AN XY: 74276

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.529

Alfa AF: 0.588 Hom.: 54469

Bravo AF: 0.500

Asia WGS AF: 0.490 AC: 1708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	10
Dann	Benign	0.83

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: rs4245660; hg19: chr1-78540733; COSMIC: COSV66127579;