rs73101660

Variant names:

• chr7-33349217-T-A
• rs73101660
• NM_198428.3:c.1432+47T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-33349217-T-A
• chr7-33349217-T-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.1432+47T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,358,850 control chromosomes in the GnomAD database, including 28,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2849 hom., cov: 32)
  • Exomes 𝑓: 0.20 (26099 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96
• Publications: 5 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=-0.89).
• BP6: Variant 7-33349217-T-A is Benign according to our data. Variant chr7-33349217-T-A is described in ClinVar as Benign. ClinVar VariationId is 263118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1432+47T>A		intron_variant	Intron 13 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1432+47T>A		intron_variant	Intron 13 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28068 AN: 152038 Hom.: 2848 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.159 AC: 39600 AN: 248450 AF XY: 0.158

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.00203

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.201 AC: 242998 AN: 1206694 Hom.: 26099 Cov.: 17 AF XY: 0.197 AC XY: 120693 AN XY: 612888

African (AFR) AF: 0.179 AC: 5042 AN: 28242

American (AMR) AF: 0.105 AC: 4648 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3461 AN: 24422

East Asian (EAS) AF: 0.000813 AC: 31 AN: 38144

South Asian (SAS) AF: 0.0803 AC: 6461 AN: 80464

European-Finnish (FIN) AF: 0.207 AC: 10743 AN: 51910

Middle Eastern (MID) AF: 0.167 AC: 876 AN: 5232

European-Non Finnish (NFE) AF: 0.229 AC: 201872 AN: 882324

Other (OTH) AF: 0.191 AC: 9864 AN: 51746

GnomAD4 genome AF: 0.185 AC: 28075 AN: 152156 Hom.: 2849 Cov.: 32 AF XY: 0.179 AC XY: 13326 AN XY: 74380

African (AFR) AF: 0.174 AC: 7217 AN: 41512

American (AMR) AF: 0.150 AC: 2291 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3468

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5184

South Asian (SAS) AF: 0.0752 AC: 363 AN: 4826

European-Finnish (FIN) AF: 0.194 AC: 2059 AN: 10594

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14953 AN: 67976

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.121 Hom.: 290

Bravo AF: 0.178

Asia WGS AF: 0.0550 AC: 191 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

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	-0.89
CADD	Benign	0.018
DANN	Benign	0.27
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs73101660; hg19: chr7-33388829;