rs12389790

chrX-81250486-G-AchrX-81250486-G-C

Variant summary

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

The NM_003022.3(SH3BGRL):c.46-26498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 110,278 control chromosomes in the GnomAD database, including 2,195 homozygotes. There are 7,272 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 0.22 (2195 hom., 7272 hem., cov: 22)
• Consequence: SH3BGRL NM_003022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

Genes affected

SH3BGRL (HGNC:10823): (SH3 domain binding glutamate rich protein like) Predicted to enable SH3 domain binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BGRL	NM_003022.3	c.46-26498G>A		intron_variant		ENST00000373212.6
SH3BGRL	XM_011531013.1	c.231+13206G>A		intron_variant
SH3BGRL	XM_011531014.2	c.156+13206G>A		intron_variant
SH3BGRL	XM_047442354.1	c.156+13206G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BGRL	ENST00000373212.6	c.46-26498G>A		intron_variant		1	NM_003022.3	P1
SH3BGRL	ENST00000481106.5	n.259-26498G>A		intron_variant, non_coding_transcript_variant		1
SH3BGRL	ENST00000463546.5	n.92-26498G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 24508 AN: 110249 Hom.: 2196 Cov.: 22 AF XY: 0.222 AC XY: 7249 AN XY: 32599

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.222 AC: 24524 AN: 110278 Hom.: 2195 Cov.: 22 AF XY: 0.223 AC XY: 7272 AN XY: 32638

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.219

Alfa AF: 0.220 Hom.: 4217

Bravo AF: 0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.0
Dann	Benign	0.51

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: rs12389790; hg19: chrX-80505985;