7-3323010-G-A

Variant names:

• chr7-3323010-G-A
• rs4343996
• NM_152744.4:c.298+21126G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152744.4(SDK1):​c.298+21126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,884 control chromosomes in the GnomAD database, including 30,104 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 0.62 (30104 hom., cov: 31)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 5 publications found

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]

SDK1-AS1 (HGNC:40883): (SDK1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4	c.298+21126G>A		intron_variant	Intron 1 of 44	ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.298+21126G>A		intron_variant	Intron 1 of 44	1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000389531.7	c.298+21126G>A		intron_variant	Intron 1 of 43	5		ENSP00000374182.3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93416 AN: 151766 Hom.: 30053 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.616 AC: 93519 AN: 151884 Hom.: 30104 Cov.: 31 AF XY: 0.607 AC XY: 45070 AN XY: 74212

African (AFR) AF: 0.825 AC: 34196 AN: 41448

American (AMR) AF: 0.511 AC: 7791 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2704 AN: 5152

South Asian (SAS) AF: 0.496 AC: 2378 AN: 4794

European-Finnish (FIN) AF: 0.474 AC: 5003 AN: 10560

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.551 AC: 37447 AN: 67918

Other (OTH) AF: 0.585 AC: 1229 AN: 2102

Alfa AF: 0.567 Hom.: 33546

Bravo AF: 0.624

Asia WGS AF: 0.571 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.45
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4343996; hg19: chr7-3362642;