chr12-32327830-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001714.4(BICD1):c.1375A>C(p.Ile459Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
BICD1
NM_001714.4 missense
NM_001714.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
BICD1 (HGNC:1049): (BICD cargo adaptor 1) This gene encodes an adaptor protein that belongs to the bicaudal D family of dynein cargo adaptors. The encoded protein acts as an intracellular cargo transport cofactor that regulates the microtubule-based loading of cargo onto the dynein motor complex. It also controls dynein motor activity and coordination. It has a domain architecture consisting of coiled-coil domains at the N- and C-termini that are highly conserved in other family members. Naturally occurring mutations in this gene are associated with short telomere length and emphysema. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09164283).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD1 | NM_001714.4 | c.1375A>C | p.Ile459Leu | missense_variant | 5/10 | ENST00000652176.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD1 | ENST00000652176.1 | c.1375A>C | p.Ile459Leu | missense_variant | 5/10 | NM_001714.4 | A1 | ||
BICD1 | ENST00000548411.6 | c.1375A>C | p.Ile459Leu | missense_variant | 5/9 | 1 | P4 | ||
BICD1 | ENST00000395758.3 | c.1375A>C | p.Ile459Leu | missense_variant, NMD_transcript_variant | 5/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250982Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135644
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461788Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727198
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74342
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2022 | The c.1375A>C (p.I459L) alteration is located in exon 5 (coding exon 5) of the BICD1 gene. This alteration results from a A to C substitution at nucleotide position 1375, causing the isoleucine (I) at amino acid position 459 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0020
.;B
Vest4
MVP
MPC
0.43
ClinPred
T
GERP RS
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at