4-122741685-T-A

Position:

• chr4-122741685-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152618.3(BBS12):​c.-10-198T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 152,304 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.030 (129 hom., cov: 33)
• Consequence: BBS12 NM_152618.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.468

Genes affected

BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-122741685-T-A is Benign according to our data. Variant chr4-122741685-T-A is described in ClinVar as [Benign]. Clinvar id is 1242472.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS12	NM_152618.3	c.-10-198T>A		intron_variant		ENST00000314218.8	NP_689831.2
BBS12	NM_001178007.2	c.-10-198T>A		intron_variant			NP_001171478.1
BBS12	XM_011531680.3	c.-10-198T>A		intron_variant			XP_011529982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS12	ENST00000314218.8	c.-10-198T>A		intron_variant		1	NM_152618.3	ENSP00000319062.3
BBS12	ENST00000542236.5	c.-10-198T>A		intron_variant		2		ENSP00000438273.1
BBS12	ENST00000433287.1	c.-10-198T>A		intron_variant		2		ENSP00000398912.1

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4527 AN: 152186 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0297 AC: 4531 AN: 152304 Hom.: 129 Cov.: 33 AF XY: 0.0285 AC XY: 2120 AN XY: 74472

Gnomad4 AFR AF: 0.0669

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0223 Hom.: 9

Bravo AF: 0.0333

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs77997891; hg19: chr4-123662840;