rs111358560

Variant names:

• chr11-66531999-G-A
• rs111358560
• NM_024649.5:c.1744G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-66531999-G-A
• chr11-66531999-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_024649.5(BBS1):​c.1744G>A​(p.Val582Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,608,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: BBS1 NM_024649.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4 B:1
• Conservation: PhyloP100: 4.88
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031392515).
• BP6: Variant 11-66531999-G-A is Benign according to our data. Variant chr11-66531999-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 305473.

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.1744G>A	p.Val582Ile	missense	Exon 17 of 17	NP_078925.3
	ZDHHC24	NM_001348571.2		c.560-2511C>T		intron	N/A	NP_001335500.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS1	ENST00000318312.12	TSL:1 MANE Select	c.1744G>A	p.Val582Ile	missense	Exon 17 of 17	ENSP00000317469.7
	ENSG00000256349	ENST00000419755.3	TSL:2	c.1855G>A	p.Val619Ile	missense	Exon 17 of 17	ENSP00000398526.3
	BBS1	ENST00000393994.4	TSL:1	c.*224G>A		3_prime_UTR	Exon 13 of 13	ENSP00000377563.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

GnomAD2 exomes AF: 0.000117 AC: 28 AN: 239438 AF XY: 0.000139

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000624

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000371

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000385 AC: 56 AN: 1456032 Hom.: 0 Cov.: 37 AF XY: 0.0000414 AC XY: 30 AN XY: 724024

African (AFR) AF: 0.0000600 AC: 2 AN: 33314

American (AMR) AF: 0.000545 AC: 24 AN: 44046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39458

South Asian (SAS) AF: 0.0000585 AC: 5 AN: 85518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.000208 AC: 1 AN: 4810

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1109956

Other (OTH) AF: 0.0000333 AC: 2 AN: 60026

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152112 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.000124 AC: 15

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	3	-	Bardet-Biedl syndrome 1 (3)
-	-	1	Bardet-Biedl syndrome (1)
-	1	-	BBS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.031	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	-1.1	N
PhyloP100		4.9
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.36	N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.10
MVP		0.63
MPC		0.12
ClinPred		0.024	T
GERP RS		2.7
Varity_R		0.075
gMVP		0.34
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs111358560; hg19: chr11-66299470; COSMIC: COSV100568103; COSMIC: COSV100568103;