rs8432

Variant names:

• chr11-66532044-A-G
• rs8432
• NM_024649.5:c.*7A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024649.5(BBS1):​c.*7A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,594,354 control chromosomes in the GnomAD database, including 286,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33640 hom., cov: 32)
  • Exomes 𝑓: 0.59 (253027 hom.)
• Consequence: BBS1 NM_024649.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.951
• Publications: 22 publications found

Genes affected

BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

ENSG00000256349 (HGNC:):

ZDHHC24 (HGNC:27387): (zinc finger DHHC-type containing 24) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-66532044-A-G is Benign according to our data. Variant chr11-66532044-A-G is described in ClinVar as Benign. ClinVar VariationId is 261745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024649.5. 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
	BBS1	NM_024649.5	MANE Select	c.*7A>G		3_prime_UTR	Exon 17 of 17	NP_078925.3
	ZDHHC24	NM_001348571.2		c.560-2556T>C		intron	N/A	NP_001335500.1	E9PLR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS1	ENST00000318312.12	TSL:1 MANE Select	c.*7A>G		3_prime_UTR	Exon 17 of 17	ENSP00000317469.7	Q8NFJ9-1
	ENSG00000256349	ENST00000419755.3	TSL:2	c.*7A>G		3_prime_UTR	Exon 17 of 17	ENSP00000398526.3
	BBS1	ENST00000393994.4	TSL:1	c.*269A>G		3_prime_UTR	Exon 13 of 13	ENSP00000377563.2	Q8NFJ9-3

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98845 AN: 151870 Hom.: 33590 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.549 AC: 119075 AN: 216906 AF XY: 0.547

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.523

Gnomad FIN exome AF: 0.649

Gnomad NFE exome AF: 0.595

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.587 AC: 846816 AN: 1442366 Hom.: 253027 Cov.: 48 AF XY: 0.583 AC XY: 417485 AN XY: 715904

African (AFR) AF: 0.865 AC: 28564 AN: 33010

American (AMR) AF: 0.367 AC: 15484 AN: 42156

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 15543 AN: 25748

East Asian (EAS) AF: 0.502 AC: 19489 AN: 38824

South Asian (SAS) AF: 0.411 AC: 34434 AN: 83760

European-Finnish (FIN) AF: 0.651 AC: 33588 AN: 51588

Middle Eastern (MID) AF: 0.587 AC: 2525 AN: 4300

European-Non Finnish (NFE) AF: 0.600 AC: 662074 AN: 1103516

Other (OTH) AF: 0.591 AC: 35115 AN: 59464

GnomAD4 genome AF: 0.651 AC: 98945 AN: 151988 Hom.: 33640 Cov.: 32 AF XY: 0.645 AC XY: 47909 AN XY: 74284

African (AFR) AF: 0.853 AC: 35359 AN: 41472

American (AMR) AF: 0.480 AC: 7335 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2080 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2651 AN: 5164

South Asian (SAS) AF: 0.408 AC: 1965 AN: 4818

European-Finnish (FIN) AF: 0.652 AC: 6900 AN: 10582

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40637 AN: 67898

Other (OTH) AF: 0.623 AC: 1318 AN: 2114

Alfa AF: 0.614 Hom.: 110385

Bravo AF: 0.649

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	Bardet-Biedl syndrome 1 (7)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.95
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: rs8432; hg19: chr11-66299515; COSMIC: COSV59153140; COSMIC: COSV59153140;