3-97786441-T-G

Variant names:

• chr3-97786441-T-G
• rs3856570
• NM_001278293.3:c.349+1392T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278293.3(ARL6):​c.349+1392T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,042 control chromosomes in the GnomAD database, including 41,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (41167 hom., cov: 32)
• Consequence: ARL6 NM_001278293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 3 publications found

Genes affected

ARL6 (HGNC:13210): (ADP ribosylation factor like GTPase 6) The protein encoded by this gene belongs to the ARF-like (ADP ribosylation factor-like) sub-family of the ARF family of GTP-binding proteins which are involved in regulation of intracellular traffic. Mutations in this gene are associated with Bardet-Biedl syndrome (BBS). A vision-specific transcript, encoding long isoform BBS3L, has been described (PMID: 20333246). [provided by RefSeq, Apr 2016]

ARL6 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• retinitis pigmentosa 55

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL6	NM_001278293.3	c.349+1392T>G		intron_variant	Intron 5 of 7	ENST00000463745.6	NP_001265222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL6	ENST00000463745.6	c.349+1392T>G		intron_variant	Intron 5 of 7	2	NM_001278293.3	ENSP00000419619.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109565 AN: 151926 Hom.: 41160 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.721 AC: 109614 AN: 152042 Hom.: 41167 Cov.: 32 AF XY: 0.727 AC XY: 54079 AN XY: 74336

African (AFR) AF: 0.488 AC: 20216 AN: 41432

American (AMR) AF: 0.807 AC: 12330 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2720 AN: 3468

East Asian (EAS) AF: 0.852 AC: 4408 AN: 5174

South Asian (SAS) AF: 0.719 AC: 3469 AN: 4826

European-Finnish (FIN) AF: 0.887 AC: 9391 AN: 10582

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54510 AN: 67980

Other (OTH) AF: 0.730 AC: 1535 AN: 2102

Alfa AF: 0.751 Hom.: 6413

Bravo AF: 0.707

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.41
PhyloP100		-2.9
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: rs3856570; hg19: chr3-97505285;