14-96382562-A-G

Variant names:

• chr14-96382562-A-G
• rs4905486
• NM_016472.5:c.258+57A>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.258+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,341,172 control chromosomes in the GnomAD database, including 27,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2316 hom., cov: 32)
  • Exomes 𝑓: 0.20 (24834 hom.)
• Consequence: GSKIP NM_016472.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.214
• Publications: 3 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=-0.91).
• BP6: Variant 14-96382562-A-G is Benign according to our data. Variant chr14-96382562-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016472.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSKIP	NM_016472.5	MANE Select	c.258+57A>G		intron	N/A	NP_057556.2	Q9P0R6
	GSKIP	NM_001271904.1		c.258+57A>G		intron	N/A	NP_001258833.1	Q9P0R6
	GSKIP	NM_001271905.2		c.258+57A>G		intron	N/A	NP_001258834.1	Q9P0R6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSKIP	ENST00000555181.6	TSL:1 MANE Select	c.258+57A>G		intron	N/A	ENSP00000450420.1	Q9P0R6
	GSKIP	ENST00000438650.5	TSL:2	c.258+57A>G		intron	N/A	ENSP00000412315.1	Q9P0R6
	GSKIP	ENST00000554182.5	TSL:2	c.258+57A>G		intron	N/A	ENSP00000451384.1	Q9P0R6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23780 AN: 152040 Hom.: 2315 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.203 AC: 241699 AN: 1189014 Hom.: 24834 AF XY: 0.203 AC XY: 120442 AN XY: 593278

African (AFR) AF: 0.0411 AC: 1078 AN: 26206

American (AMR) AF: 0.195 AC: 6113 AN: 31322

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 4304 AN: 20330

East Asian (EAS) AF: 0.207 AC: 7540 AN: 36478

South Asian (SAS) AF: 0.190 AC: 12365 AN: 65098

European-Finnish (FIN) AF: 0.162 AC: 7710 AN: 47740

Middle Eastern (MID) AF: 0.236 AC: 1181 AN: 4998

European-Non Finnish (NFE) AF: 0.211 AC: 191479 AN: 906590

Other (OTH) AF: 0.198 AC: 9929 AN: 50252

GnomAD4 genome AF: 0.156 AC: 23778 AN: 152158 Hom.: 2316 Cov.: 32 AF XY: 0.156 AC XY: 11629 AN XY: 74380

African (AFR) AF: 0.0460 AC: 1912 AN: 41546

American (AMR) AF: 0.187 AC: 2860 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3466

East Asian (EAS) AF: 0.181 AC: 937 AN: 5170

South Asian (SAS) AF: 0.175 AC: 846 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10564

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13976 AN: 67990

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.180 Hom.: 823

Bravo AF: 0.155

Asia WGS AF: 0.162 AC: 564 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.69
PhyloP100		0.21
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: rs4905486; hg19: chr14-96848899;