rs1553930514

Variant names:

• chr4-121828396-A-C
• rs1553930514
• NM_176824.3:c.1890+6T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-121828396-A-C
• chr4-121828396-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176824.3(BBS7):​c.1890+6T>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000274 in 1,458,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: BBS7 NM_176824.3 splice_region, intron
• Scores: Splicing: ADA: 0.2462
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67
• Publications: 0 publications found

Genes affected

BBS7 (HGNC:18758): (Bardet-Biedl syndrome 7) This gene encodes one of eight proteins that form the BBSome complex containing BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10. The BBSome complex is believed to recruit Rab8(GTP) to the primary cilium and promote ciliogenesis. The BBSome complex assembly is mediated by a complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins. Mutations in this gene are implicated in Bardet-Biedl syndrome, a genetic disorder whose symptoms include obesity, retinal degeneration, polydactyly and nephropathy; however, mutations in this gene and the BBS8 gene are thought to play a minor role and mutations in chaperonin-like BBS genes are found to be a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population. Two transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Oct 2014]

BBS7 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• BBS7-related ciliopathy

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176824.3. 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
	BBS7	NM_176824.3	MANE Select	c.1890+6T>G		splice_region intron	N/A	NP_789794.1	Q8IWZ6-1
	BBS7	NM_018190.4		c.1890+6T>G		splice_region intron	N/A	NP_060660.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS7	ENST00000264499.9	TSL:1 MANE Select	c.1890+6T>G		splice_region intron	N/A	ENSP00000264499.4	Q8IWZ6-1
	BBS7	ENST00000506636.1	TSL:1	c.1890+6T>G		splice_region intron	N/A	ENSP00000423626.1	Q8IWZ6-2
	BBS7	ENST00000888033.1		c.1938+6T>G		splice_region intron	N/A	ENSP00000558092.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458624 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725800

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109174

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		3.7
PromoterAI		-0.12	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.25
dbscSNV1_RF	Benign	0.52
SpliceAI score (max)		0.67		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.67		Position offset: 6

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

Other links and lift over

dbSNP: rs1553930514; hg19: chr4-122749551;