4-99280138-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000667.4(ADH1A):c.964+6T>C 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 0.0139 in 1,613,876 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0090 ( 8 hom., cov: 32)
Exomes 𝑓: 0.014 ( 194 hom. )
Consequence
ADH1A
NM_000667.4 splice_donor_region, intron
NM_000667.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.6840
2
Clinical Significance
Conservation
PhyloP100: 0.297
Genes affected
ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 4-99280138-A-G is Benign according to our data. Variant chr4-99280138-A-G is described in ClinVar as [Benign]. Clinvar id is 770906.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00903 (1376/152304) while in subpopulation NFE AF= 0.016 (1090/68022). AF 95% confidence interval is 0.0152. There are 8 homozygotes in gnomad4. There are 602 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADH1A | NM_000667.4 | c.964+6T>C | splice_donor_region_variant, intron_variant | ENST00000209668.3 | |||
LOC100507053 | NR_037884.1 | n.3790-6657A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADH1A | ENST00000209668.3 | c.964+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_000667.4 | P1 | |||
ENST00000500358.6 | n.3790-6657A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00904 AC: 1376AN: 152186Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00752 AC: 1890AN: 251396Hom.: 9 AF XY: 0.00768 AC XY: 1043AN XY: 135874
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GnomAD4 exome AF: 0.0144 AC: 21003AN: 1461572Hom.: 194 Cov.: 31 AF XY: 0.0140 AC XY: 10205AN XY: 727094
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
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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
DS_DL_spliceai
Position offset: 6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at