NM_198428.3:c.263+39A>G

Variant names:

• chr7-33152890-A-G
• rs17169881
• NM_198428.3:c.263+39A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198428.3(BBS9):​c.263+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,599,346 control chromosomes in the GnomAD database, including 28,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2142 hom., cov: 31)
  • Exomes 𝑓: 0.19 (26599 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0240
• Publications: 4 publications found

Genes affected

BBS9 (HGNC:30000): (Bardet-Biedl syndrome 9) This gene is downregulated by parathyroid hormone in osteoblastic cells, and therefore is thought to be involved in parathyroid hormone action in bones. The exact function of this gene has not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2017]

BBS9 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-33152890-A-G is Benign according to our data. Variant chr7-33152890-A-G is described in ClinVar as Benign. ClinVar VariationId is 263126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.263+39A>G		intron_variant	Intron 3 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.263+39A>G		intron_variant	Intron 3 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24598 AN: 152012 Hom.: 2137 Cov.: 31

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.190 AC: 47691 AN: 250530 AF XY: 0.194

Gnomad AFR exome AF: 0.0965

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.188 AC: 272463 AN: 1447216 Hom.: 26599 Cov.: 29 AF XY: 0.190 AC XY: 137210 AN XY: 720838

African (AFR) AF: 0.0943 AC: 3134 AN: 33240

American (AMR) AF: 0.210 AC: 9399 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4829 AN: 26030

East Asian (EAS) AF: 0.132 AC: 5226 AN: 39564

South Asian (SAS) AF: 0.234 AC: 20065 AN: 85896

European-Finnish (FIN) AF: 0.205 AC: 10894 AN: 53032

Middle Eastern (MID) AF: 0.185 AC: 1048 AN: 5676

European-Non Finnish (NFE) AF: 0.188 AC: 206814 AN: 1099204

Other (OTH) AF: 0.185 AC: 11054 AN: 59896

GnomAD4 genome AF: 0.162 AC: 24633 AN: 152130 Hom.: 2142 Cov.: 31 AF XY: 0.164 AC XY: 12170 AN XY: 74378

African (AFR) AF: 0.0982 AC: 4076 AN: 41516

American (AMR) AF: 0.178 AC: 2728 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.154 AC: 797 AN: 5166

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2202 AN: 10572

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12649 AN: 67982

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.178 Hom.: 913

Bravo AF: 0.156

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 9 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17169881; hg19: chr7-33192502; COSMIC: COSV54181849; COSMIC: COSV54181849;