rs637766

chr7-4170749-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.4801-3473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,934 control chromosomes in the GnomAD database, including 7,614 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 0.28 (7614 hom., cov: 32)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4	c.4801-3473A>G		intron_variant		ENST00000404826.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7	c.4801-3473A>G		intron_variant		1	NM_152744.4	P2
SDK1	ENST00000476701.5	n.1085-3473A>G		intron_variant, non_coding_transcript_variant		1
SDK1	ENST00000389531.7	c.4801-3473A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42234 AN: 151818 Hom.: 7601 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.278 AC: 42296 AN: 151934 Hom.: 7614 Cov.: 32 AF XY: 0.274 AC XY: 20313 AN XY: 74262

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00426

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.244

Alfa AF: 0.260 Hom.: 948

Bravo AF: 0.289

Asia WGS AF: 0.125 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.58
Dann	Benign	0.44

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: rs637766; hg19: chr7-4210381;