rs1545280

Variant names:

• chr14-96385734-T-C
• rs1545280
• NM_016472.5:c.*50T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-96385734-T-C
• chr14-96385734-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016472.5(GSKIP):​c.*50T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,450,678 control chromosomes in the GnomAD database, including 128,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (10029 hom., cov: 32)
  • Exomes 𝑓: 0.42 (118133 hom.)
• Consequence: GSKIP NM_016472.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.354
• Publications: 12 publications found

Genes affected

GSKIP (HGNC:20343): (GSK3B interacting protein) This gene encodes a protein that is involved as a negative regulator of GSK3-beta in the Wnt signaling pathway. The encoded protein may play a role in the retinoic acid signaling pathway by regulating the functional interactions between GSK3-beta, beta-catenin and cyclin D1, and it regulates the beta-catenin/N-cadherin pool. The encoded protein contains a GSK3-beta interacting domain (GID) in its C-terminus, which is similar to the GID of Axin. The protein also contains an evolutionarily conserved RII-binding domain, which facilitates binding with protein kinase-A and GSK3-beta, enabling its role as an A-kinase anchoring protein. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-96385734-T-C is Benign according to our data. Variant chr14-96385734-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSKIP	NM_016472.5	c.*50T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000555181.6	NP_057556.2
GSKIP	NM_001271904.1	c.*50T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001258833.1
GSKIP	NM_001271905.2	c.*50T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001258834.1
GSKIP	NM_001271906.2	c.*50T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001258835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSKIP	ENST00000555181.6	c.*50T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_016472.5	ENSP00000450420.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51566 AN: 151976 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.323

GnomAD2 exomes AF: 0.377 AC: 74411 AN: 197448 AF XY: 0.376

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.199

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.418 AC: 542420 AN: 1298584 Hom.: 118133 Cov.: 17 AF XY: 0.414 AC XY: 268523 AN XY: 649292

African (AFR) AF: 0.147 AC: 4159 AN: 28290

American (AMR) AF: 0.439 AC: 13821 AN: 31502

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 7632 AN: 22610

East Asian (EAS) AF: 0.193 AC: 7066 AN: 36544

South Asian (SAS) AF: 0.258 AC: 18948 AN: 73512

European-Finnish (FIN) AF: 0.417 AC: 18034 AN: 43284

Middle Eastern (MID) AF: 0.305 AC: 1600 AN: 5252

European-Non Finnish (NFE) AF: 0.449 AC: 450931 AN: 1003506

Other (OTH) AF: 0.374 AC: 20229 AN: 54084

GnomAD4 genome AF: 0.339 AC: 51575 AN: 152094 Hom.: 10029 Cov.: 32 AF XY: 0.337 AC XY: 25032 AN XY: 74370

African (AFR) AF: 0.164 AC: 6826 AN: 41500

American (AMR) AF: 0.403 AC: 6165 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3464

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5166

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4824

European-Finnish (FIN) AF: 0.408 AC: 4320 AN: 10578

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29863 AN: 67958

Other (OTH) AF: 0.320 AC: 675 AN: 2112

Alfa AF: 0.397 Hom.: 16891

Bravo AF: 0.333

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.77
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1545280; hg19: chr14-96852071; COSMIC: COSV68451324; COSMIC: COSV68451324;