rs12539695

Variant names:

• chr7-3823460-C-G
• rs12539695
• NM_152744.4:c.847+1877C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SDK1	NM_152744.4	c.847+1877C>G		intron_variant	Intron 5 of 44	ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.847+1877C>G		intron_variant	Intron 5 of 44	1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000389531.7	c.847+1877C>G		intron_variant	Intron 5 of 43	5		ENSP00000374182.3

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

African (AFR) AF: 0.164 AC: 6798 AN: 41492

American (AMR) AF: 0.200 AC: 3052 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3472

East Asian (EAS) AF: 0.0652 AC: 337 AN: 5172

South Asian (SAS) AF: 0.202 AC: 975 AN: 4824

European-Finnish (FIN) AF: 0.108 AC: 1141 AN: 10564

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11958 AN: 67982

Other (OTH) AF: 0.188 AC: 396 AN: 2110

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
PhyloP100		1.5
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: rs12539695; hg19: chr7-3863092;