rs10754220

Positions:

• chr1-197275160-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201253.3(CRB1):​c.70+6678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,764 control chromosomes in the GnomAD database, including 4,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4217 hom., cov: 31)
• Consequence: CRB1 NM_201253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

CRB1 (HGNC:2343): (crumbs cell polarity complex component 1) This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian photoreceptors. In Drosophila crumbs localizes to the stalk of the fly photoreceptor and may be a component of the molecular scaffold that controls proper development of polarity in the eye. Mutations in this gene are associated with a severe form of retinitis pigmentosa, RP12, and with Leber congenital amaurosis. Alternate splicing results in multiple transcript variants, some protein coding and some non-protein coding.[provided by RefSeq, Apr 2012]

LOC124904477 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRB1	NM_201253.3	c.70+6678G>A		intron_variant		ENST00000367400.8	NP_957705.1
LOC124904477	XR_007066780.1	n.40-1639C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRB1	ENST00000367400.8	c.70+6678G>A		intron_variant		1	NM_201253.3	ENSP00000356370	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33840 AN: 151646 Hom.: 4214 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33849 AN: 151764 Hom.: 4217 Cov.: 31 AF XY: 0.222 AC XY: 16457 AN XY: 74134

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.229

Alfa AF: 0.281 Hom.: 6044

Bravo AF: 0.216

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.77
DANN	Benign	0.46

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: rs10754220; hg19: chr1-197244290;