6-79485704-C-T

Variant names:

• chr6-79485704-C-T
• rs16890805
• NM_001122769.3:c.*1300G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001122769.3(LCA5):​c.*1300G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,190 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LCA5 NM_001122769.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0420
• Publications: 3 publications found

Genes affected

LCA5 (HGNC:31923): (lebercilin LCA5) This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described. [provided by RefSeq, Oct 2009]

LCA5 Gene-Disease associations (from GenCC):

• LCA5-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000231533 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-79485704-C-T is Benign according to our data. Variant chr6-79485704-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 358073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0256 (3900/152190) while in subpopulation SAS AF = 0.0423 (204/4820). AF 95% confidence interval is 0.0376. There are 58 homozygotes in GnomAd4. There are 1915 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122769.3. 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
	LCA5	NM_001122769.3	MANE Select	c.*1300G>A		3_prime_UTR	Exon 8 of 8	NP_001116241.1	A0A384MDJ7
	LCA5	NM_181714.4		c.*1300G>A		3_prime_UTR	Exon 9 of 9	NP_859065.2	A0A384MDJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCA5	ENST00000369846.9	TSL:1 MANE Select	c.*1300G>A		3_prime_UTR	Exon 8 of 8	ENSP00000358861.4	Q86VQ0
	LCA5	ENST00000392959.5	TSL:1	c.*1300G>A		3_prime_UTR	Exon 9 of 9	ENSP00000376686.1	Q86VQ0
	LCA5	ENST00000859359.1		c.*1300G>A		3_prime_UTR	Exon 8 of 8	ENSP00000529418.1

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3903 AN: 152072 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.00575

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0411

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0256 AC: 3900 AN: 152190 Hom.: 58 Cov.: 32 AF XY: 0.0257 AC XY: 1915 AN XY: 74414

African (AFR) AF: 0.00573 AC: 238 AN: 41538

American (AMR) AF: 0.0257 AC: 393 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0567 AC: 197 AN: 3472

East Asian (EAS) AF: 0.0395 AC: 205 AN: 5186

South Asian (SAS) AF: 0.0423 AC: 204 AN: 4820

European-Finnish (FIN) AF: 0.0224 AC: 238 AN: 10602

Middle Eastern (MID) AF: 0.0724 AC: 21 AN: 290

European-Non Finnish (NFE) AF: 0.0340 AC: 2311 AN: 67976

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0322 Hom.: 106

Bravo AF: 0.0247

Asia WGS AF: 0.0330 AC: 115 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leber congenital amaurosis 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		0.042
Mutation Taster		=100/0	polymorphism

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: rs16890805; hg19: chr6-80195421; COSMIC: COSV63972802; COSMIC: COSV63972802;