NM_024649.5:c.1719A>G

Variant names:

• chr11-66531974-A-G
• rs150553044
• NM_024649.5:c.1719A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BS2_Supporting

The NM_024649.5(BBS1):​c.1719A>G​(p.Gln573Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.000448 in 1,603,838 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00031 (2 hom.)
• Consequence: BBS1 NM_024649.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 4.14
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 11-66531974-A-G is Benign according to our data. Variant chr11-66531974-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 305472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.1719A>G	p.Gln573Gln	synonymous	Exon 17 of 17	NP_078925.3
	ZDHHC24	NM_001348571.2		c.560-2486T>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.1719A>G	p.Gln573Gln	synonymous	Exon 17 of 17	ENSP00000317469.7	Q8NFJ9-1
	ENSG00000256349	ENST00000419755.3	TSL:2	c.1830A>G	p.Gln610Gln	synonymous	Exon 17 of 17	ENSP00000398526.3
	BBS1	ENST00000393994.4	TSL:1	c.*199A>G		3_prime_UTR	Exon 13 of 13	ENSP00000377563.2	Q8NFJ9-3

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 273 AN: 152040 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

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: 0.0000883

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000568 AC: 132 AN: 232520 AF XY: 0.000485

Gnomad AFR exome AF: 0.00700

Gnomad AMR exome AF: 0.000519

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000765

Gnomad OTH exome AF: 0.000521

GnomAD4 exome AF: 0.000306 AC: 444 AN: 1451680 Hom.: 2 Cov.: 38 AF XY: 0.000286 AC XY: 206 AN XY: 721386

African (AFR) AF: 0.00834 AC: 277 AN: 33212

American (AMR) AF: 0.000533 AC: 23 AN: 43152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39190

South Asian (SAS) AF: 0.0000708 AC: 6 AN: 84794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52624

Middle Eastern (MID) AF: 0.00176 AC: 9 AN: 5102

European-Non Finnish (NFE) AF: 0.0000596 AC: 66 AN: 1107794

Other (OTH) AF: 0.00105 AC: 63 AN: 59920

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152158 Hom.: 0 Cov.: 31 AF XY: 0.00184 AC XY: 137 AN XY: 74390

African (AFR) AF: 0.00612 AC: 254 AN: 41506

American (AMR) AF: 0.000720 AC: 11 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67966

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000808 Hom.: 0

Bravo AF: 0.00232

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Bardet-Biedl syndrome 1 (3)
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.4
DANN	Benign	0.71
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism

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: rs150553044; hg19: chr11-66299445;