rs708224

Variant names:

• chr12-32283475-A-G
• rs708224
• NM_001714.4:c.427-10519A>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.427-10519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,802 control chromosomes in the GnomAD database, including 20,138 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 0.51 (20138 hom., cov: 32)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 28 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.427-10519A>G		intron_variant	Intron 2 of 9	ENST00000652176.1	NP_001705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD1	ENST00000652176.1	c.427-10519A>G		intron_variant	Intron 2 of 9		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.427-10519A>G		intron_variant	Intron 2 of 8	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.427-10519A>G		intron_variant	Intron 2 of 9	1		ENSP00000379107.3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76883 AN: 151682 Hom.: 20139 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.507 AC: 76900 AN: 151802 Hom.: 20138 Cov.: 32 AF XY: 0.505 AC XY: 37479 AN XY: 74184

African (AFR) AF: 0.371 AC: 15360 AN: 41394

American (AMR) AF: 0.500 AC: 7622 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3466

East Asian (EAS) AF: 0.453 AC: 2337 AN: 5160

South Asian (SAS) AF: 0.573 AC: 2759 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5496 AN: 10504

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39580 AN: 67900

Other (OTH) AF: 0.521 AC: 1098 AN: 2106

Alfa AF: 0.563 Hom.: 45919

Bravo AF: 0.495

Asia WGS AF: 0.493 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.64
PhyloP100		1.4
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: rs708224; hg19: chr12-32436409;