8-22547715-G-C

Variant names:

• chr8-22547715-G-C
• rs2252471
• XM_047421214.1:c.-715G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.67).
• 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 rank	MANE	Protein	UniProt
SORBS3	XM_047421214.1	c.-715G>C		splice_region_variant	Exon 2 of 23		XP_047277170.1
SORBS3	XM_047421215.1	c.-191G>C		splice_region_variant	Exon 2 of 23		XP_047277171.1
SORBS3	XM_047421216.1	c.-265G>C		splice_region_variant	Exon 2 of 24		XP_047277172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287467	ENST00000656016.2	n.188G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2
SORBS3	ENST00000522037.5	n.145-2191G>C		intron_variant	Intron 1 of 4	3
SORBS3	ENST00000523941.5	n.141-2191G>C		intron_variant	Intron 1 of 3	2
ENSG00000251034	ENST00000664810.1	n.93+5637C>G		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.525 AC: 21746 AN: 41432

American (AMR) AF: 0.535 AC: 8179 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1747 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3032 AN: 5176

South Asian (SAS) AF: 0.502 AC: 2425 AN: 4828

European-Finnish (FIN) AF: 0.443 AC: 4678 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30888 AN: 67970

Other (OTH) AF: 0.460 AC: 972 AN: 2112

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
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs2252471; hg19: chr8-22405228;