Genetic Variant BICD1:p.Lys49Ile (chr12-32107477-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001714.4(BICD1):c.146A>T(p.Lys49Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K49T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

BICD1
NM_001714.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.85

Publications

0 publications found

Variant links:

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]

BICD1 links:

BICD1-AS1 (HGNC:55475): (BICD1 antisense RNA 1)

BICD1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BICD1	NM_001714.4	MANE Select	c.146A>T	p.Lys49Ile	missense	Exon 1 of 10	NP_001705.2	Q96G01-1
BICD1	NM_001413156.1		c.146A>T	p.Lys49Ile	missense	Exon 1 of 9	NP_001400085.1
BICD1	NM_001413157.1		c.146A>T	p.Lys49Ile	missense	Exon 1 of 10	NP_001400086.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BICD1	ENST00000652176.1	MANE Select	c.146A>T	p.Lys49Ile	missense	Exon 1 of 10	ENSP00000498700.1	Q96G01-1
BICD1	ENST00000548411.6	TSL:1	c.146A>T	p.Lys49Ile	missense	Exon 1 of 9	ENSP00000446793.1	Q96G01-4
BICD1	ENST00000395758.3	TSL:1	n.146A>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243396

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.66

MutationAssessor

Pathogenic

2.9

PhyloP100

8.9

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.56

MutPred

0.33

Loss of disorder (P = 0.0018)

MVP

0.74

MPC

1.7

ClinPred

0.99

GERP RS

4.3

PromoterAI

-0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.79

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over