rs10265031

Positions:

• chr7-4182457-T-G

Variant summary

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

The NM_152744.4(SDK1):​c.5098+3871T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,164 control chromosomes in the GnomAD database, including 1,240 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 0.10 (1240 hom., cov: 33)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4	c.5098+3871T>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.5098+3871T>G		intron_variant		1	NM_152744.4	ENSP00000385899	P2
SDK1	ENST00000476701.5	n.1382+3871T>G		intron_variant, non_coding_transcript_variant		1
SDK1	ENST00000389531.7	c.5038+3871T>G		intron_variant		5		ENSP00000374182	A2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15765 AN: 152046 Hom.: 1236 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0653

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0983

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

GnomAD4 genome AF: 0.104 AC: 15785 AN: 152164 Hom.: 1240 Cov.: 33 AF XY: 0.102 AC XY: 7557 AN XY: 74394

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0654

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0977

Alfa AF: 0.0730 Hom.: 542

Bravo AF: 0.111

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs10265031; hg19: chr7-4222089;