NM_198428.3:c.1962+311G>A

Variant names:

• chr7-33384149-G-A
• rs17724206
• NM_198428.3:c.1962+311G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.1962+311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,146 control chromosomes in the GnomAD database, including 4,053 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 0.21 (4053 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1962+311G>A		intron_variant	Intron 18 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1962+311G>A		intron_variant	Intron 18 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31824 AN: 152028 Hom.: 4048 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.231

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31840 AN: 152146 Hom.: 4053 Cov.: 32 AF XY: 0.214 AC XY: 15945 AN XY: 74374

African (AFR) AF: 0.101 AC: 4214 AN: 41536

American (AMR) AF: 0.352 AC: 5371 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3470

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5178

South Asian (SAS) AF: 0.131 AC: 630 AN: 4816

European-Finnish (FIN) AF: 0.283 AC: 2989 AN: 10576

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.251 AC: 17083 AN: 67982

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.238 Hom.: 19884

Bravo AF: 0.211

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.038
DANN	Benign	0.58
PhyloP100		-1.6
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: rs17724206; hg19: chr7-33423761;