12-32308023-G-C

Variant names:

• chr12-32308023-G-C
• rs2650128
• NM_001714.4:c.1005+1901G>C

Variant summary

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

The NM_001714.4(BICD1):​c.1005+1901G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,196 control chromosomes in the GnomAD database, including 52,054 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 0.82 (52054 hom., cov: 32)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.1005+1901G>C		intron_variant	Intron 4 of 9	ENST00000652176.1	NP_001705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD1	ENST00000652176.1	c.1005+1901G>C		intron_variant	Intron 4 of 9		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.1005+1901G>C		intron_variant	Intron 4 of 8	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.1005+1901G>C		intron_variant	Intron 4 of 9	1		ENSP00000379107.3

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125251 AN: 152078 Hom.: 52022 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.823 AC: 125322 AN: 152196 Hom.: 52054 Cov.: 32 AF XY: 0.814 AC XY: 60550 AN XY: 74402

African (AFR) AF: 0.834 AC: 34613 AN: 41522

American (AMR) AF: 0.683 AC: 10435 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2907 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3101 AN: 5176

South Asian (SAS) AF: 0.717 AC: 3451 AN: 4816

European-Finnish (FIN) AF: 0.823 AC: 8718 AN: 10592

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59396 AN: 68018

Other (OTH) AF: 0.818 AC: 1729 AN: 2114

Alfa AF: 0.848 Hom.: 6430

Bravo AF: 0.811

Asia WGS AF: 0.642 AC: 2237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		-0.087
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: rs2650128; hg19: chr12-32460957;