rs12539695

chr7-3823460-C-G

Variant summary

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

The NM_152744.4(SDK1):c.847+1877C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,096 control chromosomes in the GnomAD database, including 2,314 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 0.17 (2314 hom., cov: 32)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4	c.847+1877C>G		intron_variant		ENST00000404826.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7	c.847+1877C>G		intron_variant		1	NM_152744.4	P2
SDK1	ENST00000389531.7	c.847+1877C>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25679 AN: 151978 Hom.: 2314 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.169 AC: 25703 AN: 152096 Hom.: 2314 Cov.: 32 AF XY: 0.167 AC XY: 12410 AN XY: 74384

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0652

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.188

Alfa AF: 0.171 Hom.: 279

Bravo AF: 0.176

Asia WGS AF: 0.142 AC: 496 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.3
Dann	Benign	0.31

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: rs12539695; hg19: chr7-3863092;