rs687464

Positions:

• chr7-4195719-A-G

Variant summary

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

The NM_152744.4(SDK1):​c.5099-10160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,014 control chromosomes in the GnomAD database, including 12,722 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 0.40 (12722 hom., cov: 32)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4	c.5099-10160A>G		intron_variant		ENST00000404826.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7	c.5099-10160A>G		intron_variant		1	NM_152744.4	P2
SDK1	ENST00000476701.5	n.1383-10160A>G		intron_variant, non_coding_transcript_variant		1
SDK1	ENST00000389531.7	c.5039-10160A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59980 AN: 151896 Hom.: 12691 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.395 AC: 60056 AN: 152014 Hom.: 12722 Cov.: 32 AF XY: 0.390 AC XY: 28994 AN XY: 74306

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.413

Alfa AF: 0.361 Hom.: 2057

Bravo AF: 0.402

Asia WGS AF: 0.341 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.67

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: rs687464; hg19: chr7-4235351;