rs141414233
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003922.4(HERC1):c.6225+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 1,581,242 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0054 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0075 ( 43 hom. )
Consequence
HERC1
NM_003922.4 splice_donor_region, intron
NM_003922.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00009236
2
Clinical Significance
Conservation
PhyloP100: -4.30
Genes affected
HERC1 (HGNC:4867): (HECT and RLD domain containing E3 ubiquitin protein ligase family member 1) This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
?
Variant 15-63686355-G-A is Benign according to our data. Variant chr15-63686355-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63686355-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00544 (827/152024) while in subpopulation NFE AF= 0.00957 (651/67992). AF 95% confidence interval is 0.00897. There are 1 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HERC1 | NM_003922.4 | c.6225+4C>T | splice_donor_region_variant, intron_variant | ENST00000443617.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC1 | ENST00000443617.7 | c.6225+4C>T | splice_donor_region_variant, intron_variant | 1 | NM_003922.4 | P1 | |||
ENST00000559303.2 | n.287+8036G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00544 AC: 827AN: 151908Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00527 AC: 1182AN: 224164Hom.: 5 AF XY: 0.00534 AC XY: 651AN XY: 121810
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GnomAD4 exome AF: 0.00750 AC: 10722AN: 1429218Hom.: 43 Cov.: 29 AF XY: 0.00736 AC XY: 5227AN XY: 710032
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GnomAD4 genome ? AF: 0.00544 AC: 827AN: 152024Hom.: 1 Cov.: 32 AF XY: 0.00486 AC XY: 361AN XY: 74282
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | HERC1: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 27, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at