chr4-121848809-CTCTT-C

Variant names:

• chr4-121848809-CTCTT-C
• rs111713350
• NM_176824.3:c.934+31_934+34delAAGA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_176824.3(BBS7):​c.934+31_934+34delAAGA variant causes a intron change. The variant allele was found at a frequency of 0.0391 in 1,544,376 control chromosomes in the GnomAD database, including 6,682 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (3373 hom., cov: 30)
  • Exomes 𝑓: 0.029 (3309 hom.)
• Consequence: BBS7 NM_176824.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.88
• Publications: 2 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, 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 -16 ACMG points.

• BP6: Variant 4-121848809-CTCTT-C is Benign according to our data. Variant chr4-121848809-CTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 262923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS7	NM_176824.3	c.934+31_934+34delAAGA		intron_variant	Intron 9 of 18	ENST00000264499.9	NP_789794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS7	ENST00000264499.9	c.934+31_934+34delAAGA		intron_variant	Intron 9 of 18	1	NM_176824.3	ENSP00000264499.4
BBS7	ENST00000506636.1	c.934+31_934+34delAAGA		intron_variant	Intron 9 of 17	1		ENSP00000423626.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19370 AN: 151826 Hom.: 3362 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.00511

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.0467 AC: 11618 AN: 248794 AF XY: 0.0383

Gnomad AFR exome AF: 0.406

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.0547

Gnomad EAS exome AF: 0.0307

Gnomad FIN exome AF: 0.00397

Gnomad NFE exome AF: 0.0203

Gnomad OTH exome AF: 0.0404

GnomAD4 exome AF: 0.0295 AC: 41012 AN: 1392432 Hom.: 3309 AF XY: 0.0276 AC XY: 19258 AN XY: 696846

African (AFR) AF: 0.416 AC: 13419 AN: 32234

American (AMR) AF: 0.0370 AC: 1642 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 1421 AN: 25644

East Asian (EAS) AF: 0.0244 AC: 959 AN: 39290

South Asian (SAS) AF: 0.00696 AC: 585 AN: 84108

European-Finnish (FIN) AF: 0.00521 AC: 272 AN: 52190

Middle Eastern (MID) AF: 0.0610 AC: 344 AN: 5640

European-Non Finnish (NFE) AF: 0.0186 AC: 19579 AN: 1050892

Other (OTH) AF: 0.0481 AC: 2791 AN: 58060

GnomAD4 genome AF: 0.128 AC: 19422 AN: 151944 Hom.: 3373 Cov.: 30 AF XY: 0.123 AC XY: 9132 AN XY: 74298

African (AFR) AF: 0.395 AC: 16307 AN: 41318

American (AMR) AF: 0.0691 AC: 1055 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3466

East Asian (EAS) AF: 0.0280 AC: 145 AN: 5180

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4826

European-Finnish (FIN) AF: 0.00511 AC: 54 AN: 10574

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0204 AC: 1386 AN: 67994

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0704 Hom.: 256

Bravo AF: 0.148

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Benign/Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
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: rs111713350; hg19: chr4-122769964; COSMIC: COSV99144863;