rs11514766

Positions:

• chr7-3900699-C-T

Variant summary

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

The NM_152744.4(SDK1):​c.848-50224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,984 control chromosomes in the GnomAD database, including 5,318 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 0.25 (5318 hom., cov: 32)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4	c.848-50224C>T		intron_variant		ENST00000404826.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7	c.848-50224C>T		intron_variant		1	NM_152744.4	P2
SDK1	ENST00000389531.7	c.848-50224C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37362 AN: 151866 Hom.: 5310 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.246 AC: 37416 AN: 151984 Hom.: 5318 Cov.: 32 AF XY: 0.244 AC XY: 18136 AN XY: 74292

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.253

Alfa AF: 0.216 Hom.: 1354

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.54

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: rs11514766; hg19: chr7-3940331;