12-32215232-A-G

Variant names:

• chr12-32215232-A-G
• rs161976
• NM_001714.4:c.214-1015A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001714.4(BICD1):​c.214-1015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,900 control chromosomes in the GnomAD database, including 24,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24108 hom., cov: 31)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

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.214-1015A>G		intron	N/A	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.214-1015A>G		intron	N/A	NP_001400085.1
	BICD1	NM_001413157.1		c.214-1015A>G		intron	N/A	NP_001400086.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	ENST00000652176.1	MANE Select	c.214-1015A>G		intron	N/A	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.214-1015A>G		intron	N/A	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.214-1015A>G		intron	N/A	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84515 AN: 151782 Hom.: 24092 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.557 AC: 84574 AN: 151900 Hom.: 24108 Cov.: 31 AF XY: 0.558 AC XY: 41437 AN XY: 74248

African (AFR) AF: 0.491 AC: 20348 AN: 41406

American (AMR) AF: 0.655 AC: 10010 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4242 AN: 5152

South Asian (SAS) AF: 0.685 AC: 3291 AN: 4806

European-Finnish (FIN) AF: 0.494 AC: 5207 AN: 10540

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37799 AN: 67932

Other (OTH) AF: 0.572 AC: 1209 AN: 2114

Alfa AF: 0.558 Hom.: 38877

Bravo AF: 0.563

Asia WGS AF: 0.748 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.32
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs161976; hg19: chr12-32368166;