12-32328159-G-T

Variant names:

• chr12-32328159-G-T
• rs3748275
• NM_001714.4:c.1704G>T
• BICD1 p.Val568Val

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001714.4(BICD1):​c.1704G>T​(p.Val568Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V568V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BICD1 NM_001714.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.847 with no splicing effect.

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.1704G>T	p.Val568Val	synonymous	Exon 5 of 10	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.1704G>T	p.Val568Val	synonymous	Exon 5 of 9	NP_001400085.1
	BICD1	NM_001413157.1		c.1704G>T	p.Val568Val	synonymous	Exon 5 of 10	NP_001400086.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	ENST00000652176.1	MANE Select	c.1704G>T	p.Val568Val	synonymous	Exon 5 of 10	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.1704G>T	p.Val568Val	synonymous	Exon 5 of 9	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.1704G>T		non_coding_transcript_exon	Exon 5 of 10	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.1
DANN	Benign	0.69
PhyloP100		0.85
PromoterAI		-0.022	Neutral

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

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

Other links and lift over

dbSNP: rs3748275;

hg19: chr12-32481093;