9-17633234-C-T

Variant names:

• chr9-17633234-C-T
• rs2208496
• NM_003026.5:c.45+53947C>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.45+53947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,968 control chromosomes in the GnomAD database, including 17,058 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 0.46 (17058 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 4 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]

ENSG00000298472 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003026.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	NM_003026.5	MANE Select	c.45+53947C>T		intron	N/A	NP_003017.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL2	ENST00000380607.5	TSL:1 MANE Select	c.45+53947C>T		intron	N/A	ENSP00000369981.4
	SH3GL2	ENST00000955338.1		c.45+53947C>T		intron	N/A	ENSP00000625397.1
	SH3GL2	ENST00000917907.1		c.45+53947C>T		intron	N/A	ENSP00000587966.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69791 AN: 151848 Hom.: 17061 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.459 AC: 69796 AN: 151968 Hom.: 17058 Cov.: 32 AF XY: 0.451 AC XY: 33515 AN XY: 74262

African (AFR) AF: 0.295 AC: 12231 AN: 41458

American (AMR) AF: 0.429 AC: 6543 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2196 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2186 AN: 5130

South Asian (SAS) AF: 0.326 AC: 1571 AN: 4820

European-Finnish (FIN) AF: 0.462 AC: 4872 AN: 10546

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38452 AN: 67966

Other (OTH) AF: 0.473 AC: 996 AN: 2106

Alfa AF: 0.529 Hom.: 36545

Bravo AF: 0.449

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.40
PhyloP100		-0.75
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: rs2208496; hg19: chr9-17633232; COSMIC: COSV66048718; COSMIC: COSV66048718;