chr7-3375936-A-G

Position:

• chr7-3375936-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.298+74052A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,110 control chromosomes in the GnomAD database, including 19,435 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 0.49 (19435 hom., cov: 33)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4	c.298+74052A>G		intron_variant		ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.298+74052A>G		intron_variant		1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000389531.7	c.298+74052A>G		intron_variant		5		ENSP00000374182.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74263 AN: 151992 Hom.: 19415 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.488 AC: 74304 AN: 152110 Hom.: 19435 Cov.: 33 AF XY: 0.497 AC XY: 36918 AN XY: 74356

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.508

Alfa AF: 0.543 Hom.: 10347

Bravo AF: 0.473

Asia WGS AF: 0.573 AC: 1990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1554498; hg19: chr7-3415568;