rs4418248

chr7-3381308-G-Achr7-3381308-G-T

Variant summary

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

The NM_152744.4(SDK1):c.298+79424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,038 control chromosomes in the GnomAD database, including 1,385 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 0.12 (1385 hom., cov: 31)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK1	NM_152744.4	c.298+79424G>A		intron_variant		ENST00000404826.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK1	ENST00000404826.7	c.298+79424G>A		intron_variant		1	NM_152744.4	P2
SDK1	ENST00000389531.7	c.298+79424G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18604 AN: 151920 Hom.: 1383 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.123 AC: 18632 AN: 152038 Hom.: 1385 Cov.: 31 AF XY: 0.119 AC XY: 8858 AN XY: 74332

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0941

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0898

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0959 Hom.: 1130

Bravo AF: 0.128

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.16
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4418248; hg19: chr7-3420940;