rs138194402

chr3-97784906-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001278293.3(ARL6):c.255-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,408,448 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (13 hom., cov: 32)
  • Exomes 𝑓: 0.013 (123 hom.)
• Consequence: ARL6 NM_001278293.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-97784906-A-G is Benign according to our data. Variant chr3-97784906-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 262015.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00922 (1402/152120) while in subpopulation NFE AF= 0.0152 (1032/67864). AF 95% confidence interval is 0.0144. There are 13 homozygotes in gnomad4. There are 663 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL6	NM_001278293.3	c.255-49A>G		intron_variant		ENST00000463745.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL6	ENST00000463745.6	c.255-49A>G		intron_variant		2	NM_001278293.3	P1

Frequencies

GnomAD3 genomes AF: 0.00922 AC: 1402 AN: 152002 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.00913

GnomAD3 exomes AF: 0.00887 AC: 2011 AN: 226724 Hom.: 13 AF XY: 0.00871 AC XY: 1075 AN XY: 123428

Gnomad AFR exome AF: 0.00320

Gnomad AMR exome AF: 0.00908

Gnomad ASJ exome AF: 0.00364

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000208

Gnomad FIN exome AF: 0.00264

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.00971

GnomAD4 exome AF: 0.0125 AC: 15766 AN: 1256328 Hom.: 123 Cov.: 17 AF XY: 0.0120 AC XY: 7620 AN XY: 634438

Gnomad4 AFR exome AF: 0.00240

Gnomad4 AMR exome AF: 0.00908

Gnomad4 ASJ exome AF: 0.00417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000273

Gnomad4 FIN exome AF: 0.00334

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.00922 AC: 1402 AN: 152120 Hom.: 13 Cov.: 32 AF XY: 0.00892 AC XY: 663 AN XY: 74362

Gnomad4 AFR AF: 0.00248

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00208

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.00903

Alfa AF: 0.0114 Hom.: 1

Bravo AF: 0.0102

Asia WGS AF: 0.000869 AC: 3 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.3
Dann	Benign	0.82

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: rs138194402; hg19: chr3-97503750;