rs1017874

Variant names:

• chrX-19851528-G-A
• rs1017874
• NM_031892.3:c.5-15246C>T

Variant summary

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

The NM_031892.3(SH3KBP1):​c.5-15246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 111,005 control chromosomes in the GnomAD database, including 4,035 homozygotes. There are 7,934 hemizygotes in GnomAD. 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 0.25 (4035 hom., 7934 hem., cov: 23)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 2 publications found

Genes affected

SH3KBP1 (HGNC:13867): (SH3 domain containing kinase binding protein 1) This gene encodes an adapter protein that contains one or more N-terminal Src homology domains, a proline rich region and a C-terminal coiled-coil domain. The encoded protein facilitates protein-protein interactions and has been implicated in numerous cellular processes including apoptosis, cytoskeletal rearrangement, cell adhesion and in the regulation of clathrin-dependent endocytosis. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

SH3KBP1 Gene-Disease associations (from GenCC):

• immunodeficiency 61

  Inheritance: XL, Unknown Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3KBP1	NM_031892.3	c.5-15246C>T		intron_variant	Intron 1 of 17	ENST00000397821.8	NP_114098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.5-15246C>T		intron_variant	Intron 1 of 17	1	NM_031892.3	ENSP00000380921.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 28089 AN: 110953 Hom.: 4033 Cov.: 23

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0155

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.253 AC: 28137 AN: 111005 Hom.: 4035 Cov.: 23 AF XY: 0.239 AC XY: 7934 AN XY: 33265

African (AFR) AF: 0.547 AC: 16559 AN: 30285

American (AMR) AF: 0.165 AC: 1745 AN: 10554

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 290 AN: 2642

East Asian (EAS) AF: 0.0152 AC: 54 AN: 3546

South Asian (SAS) AF: 0.0466 AC: 125 AN: 2684

European-Finnish (FIN) AF: 0.241 AC: 1435 AN: 5961

Middle Eastern (MID) AF: 0.116 AC: 25 AN: 216

European-Non Finnish (NFE) AF: 0.140 AC: 7402 AN: 52916

Other (OTH) AF: 0.244 AC: 371 AN: 1519

Alfa AF: 0.196 Hom.: 16659

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		1.2
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: rs1017874; hg19: chrX-19869646;