7-4150281-T-C

Variant names:

• chr7-4150281-T-C
• rs645106
• NM_152744.4:c.4625+818T>C

Variant summary

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

The NM_152744.4(SDK1):​c.4625+818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,066 control chromosomes in the GnomAD database, including 48,006 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 0.79 (48006 hom., cov: 33)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4	c.4625+818T>C		intron_variant	Intron 30 of 44	ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.4625+818T>C		intron_variant	Intron 30 of 44	1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000476701.5	n.909+818T>C		intron_variant	Intron 4 of 19	1
SDK1	ENST00000389531.7	c.4625+818T>C		intron_variant	Intron 30 of 43	5		ENSP00000374182.3

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119733 AN: 151948 Hom.: 47935 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.788 AC: 119859 AN: 152066 Hom.: 48006 Cov.: 33 AF XY: 0.790 AC XY: 58689 AN XY: 74306

African (AFR) AF: 0.947 AC: 39367 AN: 41562

American (AMR) AF: 0.777 AC: 11878 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2602 AN: 3470

East Asian (EAS) AF: 0.785 AC: 4010 AN: 5110

South Asian (SAS) AF: 0.684 AC: 3293 AN: 4814

European-Finnish (FIN) AF: 0.751 AC: 7938 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48322 AN: 67942

Other (OTH) AF: 0.772 AC: 1633 AN: 2116

Alfa AF: 0.733 Hom.: 4360

Bravo AF: 0.797

Asia WGS AF: 0.795 AC: 2765 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	2.6
DANN	Benign	0.40
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs645106; hg19: chr7-4189913;