8-22547715-G-C

Position:

• chr8-22547715-G-C

Variant summary

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

The XM_047421214.1(SORBS3):​c.-715G>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,040 control chromosomes in the GnomAD database, including 18,384 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 0.49 (18384 hom., cov: 32)
• Consequence: SORBS3 XM_047421214.1 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS3	XM_047421214.1	c.-715G>C		splice_region_variant	2/23		XP_047277170.1
SORBS3	XM_047421215.1	c.-191G>C		splice_region_variant	2/23		XP_047277171.1
SORBS3	XM_047421216.1	c.-265G>C		splice_region_variant	2/24		XP_047277172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000287467	ENST00000656016.1	n.168G>C		splice_region_variant, non_coding_transcript_exon_variant	2/2
SORBS3	ENST00000522037.5	n.145-2191G>C		intron_variant		3
SORBS3	ENST00000523941.5	n.141-2191G>C		intron_variant		2
ENSG00000251034	ENST00000664810.1	n.93+5637C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74251 AN: 151922 Hom.: 18376 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.489 AC: 74302 AN: 152040 Hom.: 18384 Cov.: 32 AF XY: 0.490 AC XY: 36450 AN XY: 74320

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.460

Alfa AF: 0.472 Hom.: 2155

Bravo AF: 0.495

Asia WGS AF: 0.502 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.5
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2252471; hg19: chr8-22405228;