12-32327830-ATC-TTG

Variant names:

• chr12-32327830-ATC-TTG
• NM_001714.4:c.1375_1377delATCinsTTG
• BICD1 p.Ile459Leu

Variant summary

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

The NM_001714.4(BICD1):​c.1375_1377delATCinsTTG​(p.Ile459Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BICD1 NM_001714.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	NM_001714.4	MANE Select	c.1375_1377delATCinsTTG	p.Ile459Leu	missense	N/A	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.1375_1377delATCinsTTG	p.Ile459Leu	missense	N/A	NP_001400085.1
	BICD1	NM_001413157.1		c.1375_1377delATCinsTTG	p.Ile459Leu	missense	N/A	NP_001400086.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	ENST00000652176.1	MANE Select	c.1375_1377delATCinsTTG	p.Ile459Leu	missense	N/A	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.1375_1377delATCinsTTG	p.Ile459Leu	missense	N/A	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.1375_1377delATCinsTTG		non_coding_transcript_exon	Exon 5 of 10	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-32480764;