chr7-4206002-C-T

Variant names:

• chr7-4206002-C-T
• rs193920905
• NM_152744.4:c.5214+8C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152744.4(SDK1):​c.5214+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,365,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SDK1 NM_152744.4 splice_region, intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.909
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4	c.5214+8C>T		splice_region_variant, intron_variant	Intron 36 of 44	ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.5214+8C>T		splice_region_variant, intron_variant	Intron 36 of 44	1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000476701.5	n.1498+8C>T		splice_region_variant, intron_variant	Intron 10 of 19	1
SDK1	ENST00000389531.7	c.5154+8C>T		splice_region_variant, intron_variant	Intron 35 of 43	5		ENSP00000374182.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1365566 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 671118

African (AFR) AF: 0.0000326 AC: 1 AN: 30718

American (AMR) AF: 0.00 AC: 0 AN: 32956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22998

East Asian (EAS) AF: 0.00 AC: 0 AN: 35120

South Asian (SAS) AF: 0.00 AC: 0 AN: 74698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058956

Other (OTH) AF: 0.00 AC: 0 AN: 56602

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.041
DANN	Benign	0.56
PhyloP100		-0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs193920905; hg19: chr7-4245634;