7-33336534-C-T

Variant names:

• chr7-33336534-C-T
• rs61753524
• NM_198428.3:c.1110C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001348041.4(BBS9):​c.1110C>T​(p.Asn370Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000968 in 1,613,156 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (5 hom.)
• Consequence: BBS9 NM_001348041.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.188
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 7-33336534-C-T is Benign according to our data. Variant chr7-33336534-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.188 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00496 (756/152266) while in subpopulation AFR AF = 0.0172 (715/41538). AF 95% confidence interval is 0.0162. There are 6 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348041.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.1110C>T	p.Asn370Asn	synonymous	Exon 10 of 23	NP_940820.1
	BBS9	NM_001348041.4		c.1110C>T	p.Asn370Asn	synonymous	Exon 10 of 23	NP_001334970.1
	BBS9	NM_001348036.1		c.1110C>T	p.Asn370Asn	synonymous	Exon 10 of 23	NP_001334965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.1110C>T	p.Asn370Asn	synonymous	Exon 10 of 23	ENSP00000242067.6
	BBS9	ENST00000433714.5	TSL:1	n.1110C>T		non_coding_transcript_exon	Exon 10 of 24	ENSP00000412159.1
	BBS9	ENST00000942912.1		c.1236C>T	p.Asn412Asn	synonymous	Exon 11 of 24	ENSP00000612971.1

Frequencies

GnomAD3 genomes AF: 0.00497 AC: 756 AN: 152150 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00145 AC: 363 AN: 250688 AF XY: 0.00106

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.000899

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000551 AC: 805 AN: 1460890 Hom.: 5 Cov.: 30 AF XY: 0.000451 AC XY: 328 AN XY: 726766

African (AFR) AF: 0.0183 AC: 614 AN: 33462

American (AMR) AF: 0.000940 AC: 42 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1111314

Other (OTH) AF: 0.00108 AC: 65 AN: 60342

GnomAD4 genome AF: 0.00496 AC: 756 AN: 152266 Hom.: 6 Cov.: 32 AF XY: 0.00513 AC XY: 382 AN XY: 74444

African (AFR) AF: 0.0172 AC: 715 AN: 41538

American (AMR) AF: 0.00190 AC: 29 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00195 Hom.: 7

Bravo AF: 0.00609

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Bardet-Biedl syndrome 9 (2)
-	-	2	not specified (2)
-	-	1	Bardet-Biedl syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.6
DANN	Benign	0.42
PhyloP100		0.19
Mutation Taster		=99/1	polymorphism

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: rs61753524; hg19: chr7-33376146;