17-72120683-G-GCGCACA

Variant names:

• chr17-72120683-G-GCGCACA
• rs3837814
• ENST00000533232.5:n.31+79_31+80insTGTGCG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000533232.5(SOX9-AS1):​n.31+79_31+80insTGTGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00857 in 151,040 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (15 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (0 hom.)
• Consequence: SOX9-AS1 ENST00000533232.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.511
• Publications: 0 publications found

Genes affected

SOX9-AS1 (HGNC:49321): (SOX9 antisense RNA 1)

ENSG00000288605 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 17-72120683-G-GCGCACA is Benign according to our data. Variant chr17-72120683-G-GCGCACA is described in ClinVar as Likely_benign. ClinVar VariationId is 1199135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9-AS1	NR_103737.1		n.31+79_31+80insTGTGCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9-AS1	ENST00000533232.5	TSL:1	n.31+79_31+80insTGTGCG		intron	N/A
	SOX9-AS1	ENST00000414600.1	TSL:3	n.96+21001_96+21002insTGTGCG		intron	N/A
	ENSG00000288605	ENST00000628742.2	TSL:5	n.147-35639_147-35638insTGTGCG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00862 AC: 1285 AN: 149026 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.00642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00842

Gnomad EAS AF: 0.00561

Gnomad SAS AF: 0.00578

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00643

Gnomad OTH AF: 0.00975

GnomAD4 exome AF: 0.00364 AC: 7 AN: 1922 Hom.: 0 AF XY: 0.00447 AC XY: 4 AN XY: 894

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 86

American (AMR) AF: 0.00 AC: 0 AN: 48

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 162

East Asian (EAS) AF: 0.00843 AC: 3 AN: 356

South Asian (SAS) AF: 0.111 AC: 2 AN: 18

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00185 AC: 2 AN: 1080

Other (OTH) AF: 0.00 AC: 0 AN: 146

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000221067), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00864 AC: 1288 AN: 149118 Hom.: 15 Cov.: 0 AF XY: 0.00938 AC XY: 681 AN XY: 72588

African (AFR) AF: 0.00641 AC: 261 AN: 40742

American (AMR) AF: 0.0161 AC: 242 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00842 AC: 29 AN: 3444

East Asian (EAS) AF: 0.00583 AC: 29 AN: 4976

South Asian (SAS) AF: 0.00600 AC: 28 AN: 4664

European-Finnish (FIN) AF: 0.0248 AC: 248 AN: 10012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00643 AC: 431 AN: 67002

Other (OTH) AF: 0.00964 AC: 20 AN: 2074

Alfa AF: 0.00587 Hom.: 349

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3837814; hg19: chr17-70116824;