rs4578059

Variant names:

• chr9-17673049-C-T
• rs4578059
• NM_003026.5:c.46-74017C>T

Variant summary

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

The NM_003026.5(SH3GL2):​c.46-74017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,924 control chromosomes in the GnomAD database, including 20,310 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 0.50 (20310 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 0 publications found

Genes affected

SH3GL2 (HGNC:10831): (SH3 domain containing GRB2 like 2, endophilin A1) Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of protein phosphorylation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3GL2	NM_003026.5	c.46-74017C>T		intron_variant	Intron 1 of 8	ENST00000380607.5	NP_003017.1
SH3GL2	XM_011518005.4	c.147+54834C>T		intron_variant	Intron 1 of 8		XP_011516307.1
SH3GL2	XM_047423730.1	c.-61+65795C>T		intron_variant	Intron 1 of 8		XP_047279686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3GL2	ENST00000380607.5	c.46-74017C>T		intron_variant	Intron 1 of 8	1	NM_003026.5	ENSP00000369981.4

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76412 AN: 151806 Hom.: 20279 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.504 AC: 76498 AN: 151924 Hom.: 20310 Cov.: 32 AF XY: 0.510 AC XY: 37860 AN XY: 74270

African (AFR) AF: 0.652 AC: 26987 AN: 41416

American (AMR) AF: 0.596 AC: 9099 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2688 AN: 5130

South Asian (SAS) AF: 0.506 AC: 2437 AN: 4818

European-Finnish (FIN) AF: 0.484 AC: 5110 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.404 AC: 27480 AN: 67960

Other (OTH) AF: 0.490 AC: 1031 AN: 2106

Alfa AF: 0.477 Hom.: 2267

Bravo AF: 0.520

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		-0.057
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: rs4578059; hg19: chr9-17673047; COSMIC: COSV66054911;