rs34912216

Positions:

• chr7-4078745-G-A

Variant summary

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

The NM_152744.4(SDK1):​c.3203-718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,082 control chromosomes in the GnomAD database, including 12,395 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 0.36 (12395 hom., cov: 32)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4	c.3203-718G>A		intron_variant		ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.3203-718G>A		intron_variant		1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000389531.7	c.3203-718G>A		intron_variant		5		ENSP00000374182.3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55442 AN: 151964 Hom.: 12380 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.365 AC: 55499 AN: 152082 Hom.: 12395 Cov.: 32 AF XY: 0.358 AC XY: 26606 AN XY: 74346

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.322

Alfa AF: 0.330 Hom.: 1238

Bravo AF: 0.373

Asia WGS AF: 0.224 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34912216; hg19: chr7-4118377;