rs4723454

Variant names:

• chr7-4200453-A-C
• rs4723454
• NM_152744.4:c.5099-5426A>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.5099-5426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,182 control chromosomes in the GnomAD database, including 10,716 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 0.36 (10716 hom., cov: 33)
• Consequence: SDK1 NM_152744.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 6 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 = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4	c.5099-5426A>C		intron_variant	Intron 35 of 44	ENST00000404826.7	NP_689957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.5099-5426A>C		intron_variant	Intron 35 of 44	1	NM_152744.4	ENSP00000385899.2
SDK1	ENST00000476701.5	n.1383-5426A>C		intron_variant	Intron 9 of 19	1
SDK1	ENST00000389531.7	c.5039-5426A>C		intron_variant	Intron 34 of 43	5		ENSP00000374182.3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55452 AN: 152066 Hom.: 10689 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.365 AC: 55517 AN: 152182 Hom.: 10716 Cov.: 33 AF XY: 0.364 AC XY: 27100 AN XY: 74422

African (AFR) AF: 0.493 AC: 20449 AN: 41486

American (AMR) AF: 0.298 AC: 4562 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1102 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1329 AN: 5180

South Asian (SAS) AF: 0.404 AC: 1949 AN: 4822

European-Finnish (FIN) AF: 0.297 AC: 3143 AN: 10594

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21680 AN: 68014

Other (OTH) AF: 0.386 AC: 817 AN: 2114

Alfa AF: 0.337 Hom.: 34145

Bravo AF: 0.371

Asia WGS AF: 0.303 AC: 1054 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	0.50
PhyloP100		-0.29
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: rs4723454; hg19: chr7-4240085;