chr19-47834259-T-C

Variant names:

• chr19-47834259-T-C
• rs4801737
• NM_000554.6:c.-35-150T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000554.6(CRX):​c.-35-150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 645,826 control chromosomes in the GnomAD database, including 3,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1948 hom., cov: 31)
  • Exomes 𝑓: 0.067 (1881 hom.)
• Consequence: CRX NM_000554.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.218

Genes affected

CRX (HGNC:2383): (cone-rod homeobox) The protein encoded by this gene is a photoreceptor-specific transcription factor which plays a role in the differentiation of photoreceptor cells. This homeodomain protein is necessary for the maintenance of normal cone and rod function. Mutations in this gene are associated with photoreceptor degeneration, Leber congenital amaurosis type III and the autosomal dominant cone-rod dystrophy 2. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-47834259-T-C is Benign according to our data. Variant chr19-47834259-T-C is described in ClinVar as [Benign]. Clinvar id is 1243300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRX	NM_000554.6	c.-35-150T>C		intron_variant	Intron 1 of 3	ENST00000221996.12	NP_000545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRX	ENST00000221996.12	c.-35-150T>C		intron_variant	Intron 1 of 3	2	NM_000554.6	ENSP00000221996.5
CRX	ENST00000556527.1	n.78-1984T>C		intron_variant	Intron 1 of 1	1
CRX	ENST00000566686.5	c.-35-150T>C		intron_variant	Intron 1 of 2	5		ENSP00000457808.2
CRX	ENST00000613299.1	c.-35-150T>C		intron_variant	Intron 1 of 2	3		ENSP00000478106.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18161 AN: 152064 Hom.: 1939 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0673 AC: 33210 AN: 493644 Hom.: 1881 AF XY: 0.0699 AC XY: 18382 AN XY: 262966

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.0572

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.000419

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0286

Gnomad4 NFE exome AF: 0.0527

Gnomad4 OTH exome AF: 0.0850

GnomAD4 genome AF: 0.120 AC: 18206 AN: 152182 Hom.: 1948 Cov.: 31 AF XY: 0.119 AC XY: 8838 AN XY: 74414

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.0807

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0627 Hom.: 205

Bravo AF: 0.132

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4801737; hg19: chr19-48337516;