chr12-32327816-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001714.4(BICD1):āc.1361A>Cā(p.Lys454Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000601 in 1,614,048 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 Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000065 ( 0 hom. )
Consequence
BICD1
NM_001714.4 missense
NM_001714.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 7.17
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=0.13005215).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD1 | NM_001714.4 | c.1361A>C | p.Lys454Thr | missense_variant | 5/10 | ENST00000652176.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD1 | ENST00000652176.1 | c.1361A>C | p.Lys454Thr | missense_variant | 5/10 | NM_001714.4 | A1 | ||
BICD1 | ENST00000548411.6 | c.1361A>C | p.Lys454Thr | missense_variant | 5/9 | 1 | P4 | ||
BICD1 | ENST00000395758.3 | c.1361A>C | p.Lys454Thr | missense_variant, NMD_transcript_variant | 5/10 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 250980Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135644
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GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.0000756 AC XY: 55AN XY: 727202
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74394
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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 24, 2023 | The c.1361A>C (p.K454T) 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 1361, causing the lysine (K) at amino acid position 454 to be replaced by a threonine (T). 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
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
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
Uncertain
D;T
Sift4G
Benign
T;T
Polyphen
0.91
.;P
Vest4
MutPred
Loss of ubiquitination at K454 (P = 0.0067);Loss of ubiquitination at K454 (P = 0.0067);
MVP
MPC
1.2
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