chr6-75922180-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001563.4(IMPG1):​c.2317-14T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000995 in 1,004,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

IMPG1
NM_001563.4 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.351
Variant links:
Genes affected
IMPG1 (HGNC:6055): (interphotoreceptor matrix proteoglycan 1) This gene encodes a protein that is a major component of the retinal interphotoreceptor matrix. The encoded protein is a proteoglycan that is thought to play a role in maintaining viability of photoreceptor cells and in adhesion of the neural retina to the retinal pigment epithelium. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 6-75922180-A-C is Benign according to our data. Variant chr6-75922180-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1900890.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IMPG1NM_001563.4 linkuse as main transcriptc.2317-14T>G splice_polypyrimidine_tract_variant, intron_variant ENST00000369950.8
IMPG1NM_001282368.2 linkuse as main transcriptc.2083-14T>G splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IMPG1ENST00000369950.8 linkuse as main transcriptc.2317-14T>G splice_polypyrimidine_tract_variant, intron_variant 1 NM_001563.4 P2Q17R60-1
IMPG1ENST00000369952.3 linkuse as main transcriptc.400-14T>G splice_polypyrimidine_tract_variant, intron_variant 3
IMPG1ENST00000611179.4 linkuse as main transcriptc.2083-14T>G splice_polypyrimidine_tract_variant, intron_variant 5 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.95e-7
AC:
1
AN:
1004972
Hom.:
0
Cov.:
14
AF XY:
0.00000195
AC XY:
1
AN XY:
513726
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000140
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 04, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
8.5
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-76631897; API