rs8142

Variant names:

• chr15-68207323-G-A
• rs8142
• NM_017882.3:c.*817C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-68207323-G-A
• chr15-68207323-G-C

Variant summary

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

The NM_017882.3(CLN6):​c.*817C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,448 control chromosomes in the GnomAD database, including 19,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19701 hom., cov: 34)
  • Exomes 𝑓: 0.54 (46 hom.)
• Consequence: CLN6 NM_017882.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.84
• Publications: 11 publications found

Genes affected

CLN6 (HGNC:2077): (CLN6 transmembrane ER protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function. [provided by RefSeq, Oct 2008]

CLN6 Gene-Disease associations (from GenCC):

• ceroid lipofuscinosis, neuronal, 6A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, Genomics England PanelApp, G2P
• ceroid lipofuscinosis, neuronal, 6B (Kufs type)

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp
• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000260007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-68207323-G-A is Benign according to our data. Variant chr15-68207323-G-A is described in ClinVar as Benign. ClinVar VariationId is 316970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017882.3. 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
	CLN6	NM_017882.3	MANE Select	c.*817C>T		3_prime_UTR	Exon 7 of 7	NP_060352.1	Q9NWW5-1
	CLN6	NM_001411068.1		c.*817C>T		3_prime_UTR	Exon 7 of 7	NP_001397997.1	Q9NWW5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLN6	ENST00000249806.11	TSL:1 MANE Select	c.*817C>T		3_prime_UTR	Exon 7 of 7	ENSP00000249806.5	Q9NWW5-1
	ENSG00000260007	ENST00000562767.2	TSL:3	c.84-9695C>T		intron	N/A	ENSP00000456336.1	H3BRN7
	ENSG00000260007	ENST00000638026.1	TSL:1	n.358C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76286 AN: 152026 Hom.: 19684 Cov.: 34

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.536 AC: 162 AN: 302 Hom.: 46 Cov.: 0 AF XY: 0.533 AC XY: 113 AN XY: 212

African (AFR) AF: 0.875 AC: 7 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.333 AC: 2 AN: 6

European-Finnish (FIN) AF: 0.385 AC: 10 AN: 26

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.556 AC: 130 AN: 234

Other (OTH) AF: 0.450 AC: 9 AN: 20

GnomAD4 genome AF: 0.502 AC: 76338 AN: 152146 Hom.: 19701 Cov.: 34 AF XY: 0.494 AC XY: 36744 AN XY: 74366

African (AFR) AF: 0.469 AC: 19465 AN: 41510

American (AMR) AF: 0.502 AC: 7668 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3472

East Asian (EAS) AF: 0.176 AC: 910 AN: 5170

South Asian (SAS) AF: 0.349 AC: 1685 AN: 4826

European-Finnish (FIN) AF: 0.513 AC: 5427 AN: 10576

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37822 AN: 67984

Other (OTH) AF: 0.510 AC: 1078 AN: 2112

Alfa AF: 0.509 Hom.: 8590

Bravo AF: 0.501

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neuronal ceroid lipofuscinosis (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.77
PhyloP100		-1.8
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: rs8142; hg19: chr15-68499661;