rs2280890

Variant names:

• chr8-22547327-C-T
• rs2280890
• ENST00000522037.5:n.144+2198C>T

Variant summary

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

The ENST00000522037.5(SORBS3):​n.144+2198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00992 in 146,940 control chromosomes in the GnomAD database, including 28 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 0.0099 (28 hom., cov: 29)
• Consequence: SORBS3 ENST00000522037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 10 publications found

Genes affected

SORBS3 (HGNC:30907): (sorbin and SH3 domain containing 3) This gene encodes an SH3 domain-containing adaptor protein. The presence of SH3 domains play a role in this protein's ability to bind other cytoplasmic molecules and contribute to cystoskeletal organization, cell adhesion and migration, signaling, and gene expression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ENSG00000287467 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS3	XM_047421213.1	c.-47+2198C>T		intron_variant	Intron 1 of 21		XP_047277169.1
SORBS3	XM_047421214.1	c.-716-387C>T		intron_variant	Intron 1 of 22		XP_047277170.1
SORBS3	XM_047421215.1	c.-192-387C>T		intron_variant	Intron 1 of 22		XP_047277171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS3	ENST00000522037.5	n.144+2198C>T		intron_variant	Intron 1 of 4	3
SORBS3	ENST00000523941.5	n.140+2198C>T		intron_variant	Intron 1 of 3	2
ENSG00000287467	ENST00000656016.2	n.187-387C>T		intron_variant	Intron 1 of 1
ENSG00000251034	ENST00000664810.1	n.93+6025G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00980 AC: 1439 AN: 146858 Hom.: 28 Cov.: 29

Gnomad AFR AF: 0.00771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.00263

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.00178

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.00233

Gnomad OTH AF: 0.0128

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

GnomAD4 genome AF: 0.00992 AC: 1458 AN: 146940 Hom.: 28 Cov.: 29 AF XY: 0.0109 AC XY: 777 AN XY: 71434

African (AFR) AF: 0.00781 AC: 313 AN: 40056

American (AMR) AF: 0.0245 AC: 365 AN: 14884

Ashkenazi Jewish (ASJ) AF: 0.00263 AC: 9 AN: 3424

East Asian (EAS) AF: 0.0853 AC: 436 AN: 5114

South Asian (SAS) AF: 0.0267 AC: 125 AN: 4686

European-Finnish (FIN) AF: 0.00178 AC: 16 AN: 8994

Middle Eastern (MID) AF: 0.0143 AC: 4 AN: 280

European-Non Finnish (NFE) AF: 0.00233 AC: 155 AN: 66550

Other (OTH) AF: 0.0171 AC: 35 AN: 2052

Alfa AF: 0.00562 Hom.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.30
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2280890; hg19: chr8-22404840;