rs77010939

Variant names:

• chr3-97791763-C-T
• rs77010939
• NM_001278293.3:c.480-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-97791763-C-T
• chr3-97791763-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001278293.3(ARL6):​c.480-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,613,100 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (49 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (47 hom.)
• Consequence: ARL6 NM_001278293.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001035
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.76
• Publications: 1 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 55

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-97791763-C-T is Benign according to our data. Variant chr3-97791763-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6	NM_001278293.3	MANE Select	c.480-8C>T		splice_region intron	N/A	NP_001265222.1	Q9H0F7-1
	ARL6	NM_001323513.2		c.480-8C>T		splice_region intron	N/A	NP_001310442.1	Q9H0F7-2
	ARL6	NM_032146.5		c.480-8C>T		splice_region intron	N/A	NP_115522.1	Q9H0F7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6	ENST00000463745.6	TSL:2 MANE Select	c.480-8C>T		splice_region intron	N/A	ENSP00000419619.1	Q9H0F7-1
	ARL6	ENST00000493990.5	TSL:1	n.480-8C>T		splice_region intron	N/A	ENSP00000418057.1	Q9H0F7-1
	ARL6	ENST00000631834.2	TSL:4	c.480-8C>T		splice_region intron	N/A	ENSP00000488530.2	Q9H0F7-2

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2098 AN: 152082 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00391 AC: 982 AN: 251122 AF XY: 0.00284

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00153 AC: 2229 AN: 1460900 Hom.: 47 Cov.: 30 AF XY: 0.00140 AC XY: 1017 AN XY: 726798

African (AFR) AF: 0.0531 AC: 1773 AN: 33414

American (AMR) AF: 0.00192 AC: 86 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00131 AC: 113 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5756

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1111404

Other (OTH) AF: 0.00315 AC: 190 AN: 60350

GnomAD4 genome AF: 0.0138 AC: 2099 AN: 152200 Hom.: 49 Cov.: 32 AF XY: 0.0133 AC XY: 991 AN XY: 74420

African (AFR) AF: 0.0483 AC: 2004 AN: 41522

American (AMR) AF: 0.00425 AC: 65 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00600 Hom.: 14

Bravo AF: 0.0164

Asia WGS AF: 0.00405 AC: 14 AN: 3474

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Bardet-Biedl syndrome 3 (1)
-	-	1	Bardet-Biedl syndrome 3;C3150808:Retinitis pigmentosa 55 (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.6
DANN	Benign	0.41
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000010
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs77010939; hg19: chr3-97510607;