rs2280890

Positions:

• chr8-22547327-C-T

Variant summary

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

The ENST00000656016.1(ENSG00000287467):​n.167-387C>T variant causes a intron, non coding transcript 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: ENST00000656016.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC124901905	XR_007060851.1	n.1964+4835G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000656016.1	n.167-387C>T		intron_variant, non_coding_transcript_variant
	ENST00000664810.1	n.93+6025G>A		intron_variant, non_coding_transcript_variant
SORBS3	ENST00000522037.5	n.144+2198C>T		intron_variant, non_coding_transcript_variant		3
SORBS3	ENST00000523941.5	n.140+2198C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.00781

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.00263

Gnomad4 EAS AF: 0.0853

Gnomad4 SAS AF: 0.0267

Gnomad4 FIN AF: 0.00178

Gnomad4 NFE AF: 0.00233

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.00523 Hom.: 24

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280890; hg19: chr8-22404840;