12-32310081-T-G

Variant names:

• chr12-32310081-T-G
• rs261900
• NM_001714.4:c.1005+3959T>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.1005+3959T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,056 control chromosomes in the GnomAD database, including 31,278 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 0.63 (31278 hom., cov: 32)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.1005+3959T>G		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+3959T>G		intron_variant	Intron 4 of 9		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.1005+3959T>G		intron_variant	Intron 4 of 8	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.1005+3959T>G		intron_variant	Intron 4 of 9	1		ENSP00000379107.3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96392 AN: 151938 Hom.: 31260 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.634 AC: 96441 AN: 152056 Hom.: 31278 Cov.: 32 AF XY: 0.623 AC XY: 46309 AN XY: 74306

African (AFR) AF: 0.702 AC: 29104 AN: 41482

American (AMR) AF: 0.536 AC: 8181 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2343 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1429 AN: 5166

South Asian (SAS) AF: 0.594 AC: 2859 AN: 4816

European-Finnish (FIN) AF: 0.553 AC: 5833 AN: 10556

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44592 AN: 67978

Other (OTH) AF: 0.634 AC: 1337 AN: 2108

Alfa AF: 0.644 Hom.: 45243

Bravo AF: 0.632

Asia WGS AF: 0.445 AC: 1551 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	0.64
DANN	Benign	0.55
PhyloP100		-0.22
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: rs261900; hg19: chr12-32463015;