chr3-97768395-C-T

Variant names:

• chr3-97768395-C-T
• rs1567058
• NM_001278293.3:c.123+165C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001278293.3(ARL6):​c.123+165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,014 control chromosomes in the GnomAD database, including 46,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (46597 hom., cov: 33)
• Consequence: ARL6 NM_001278293.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.340
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-97768395-C-T is Benign according to our data. Variant chr3-97768395-C-T is described in ClinVar as Benign. ClinVar VariationId is 1281373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6	NM_001278293.3	MANE Select	c.123+165C>T		intron	N/A	NP_001265222.1
	ARL6	NM_001323513.2		c.123+165C>T		intron	N/A	NP_001310442.1
	ARL6	NM_032146.5		c.123+165C>T		intron	N/A	NP_115522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6	ENST00000463745.6	TSL:2 MANE Select	c.123+165C>T		intron	N/A	ENSP00000419619.1
	ARL6	ENST00000493990.5	TSL:1	n.123+165C>T		intron	N/A	ENSP00000418057.1
	ARL6	ENST00000496713.1	TSL:1	n.361+165C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118818 AN: 151896 Hom.: 46555 Cov.: 33

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.782 AC: 118921 AN: 152014 Hom.: 46597 Cov.: 33 AF XY: 0.786 AC XY: 58368 AN XY: 74300

African (AFR) AF: 0.779 AC: 32335 AN: 41482

American (AMR) AF: 0.827 AC: 12636 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2686 AN: 3464

East Asian (EAS) AF: 0.851 AC: 4411 AN: 5186

South Asian (SAS) AF: 0.694 AC: 3348 AN: 4824

European-Finnish (FIN) AF: 0.835 AC: 8831 AN: 10578

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 51967 AN: 67874

Other (OTH) AF: 0.789 AC: 1667 AN: 2114

Alfa AF: 0.776 Hom.: 15631

Bravo AF: 0.784

Asia WGS AF: 0.806 AC: 2799 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.15
PhyloP100		0.34
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: rs1567058; hg19: chr3-97487239;