12-32265317-T-C

Variant names:

• chr12-32265317-T-C
• rs161981
• NM_001714.4:c.427-28677T>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.427-28677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,936 control chromosomes in the GnomAD database, including 26,241 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 0.58 (26241 hom., cov: 31)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.427-28677T>C		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.427-28677T>C		intron_variant	Intron 2 of 9		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.427-28677T>C		intron_variant	Intron 2 of 8	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.427-28677T>C		intron_variant	Intron 2 of 9	1		ENSP00000379107.3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88415 AN: 151816 Hom.: 26209 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.583 AC: 88504 AN: 151936 Hom.: 26241 Cov.: 31 AF XY: 0.580 AC XY: 43076 AN XY: 74254

African (AFR) AF: 0.686 AC: 28410 AN: 41428

American (AMR) AF: 0.502 AC: 7660 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3468

East Asian (EAS) AF: 0.684 AC: 3529 AN: 5160

South Asian (SAS) AF: 0.588 AC: 2827 AN: 4810

European-Finnish (FIN) AF: 0.521 AC: 5489 AN: 10528

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37097 AN: 67966

Other (OTH) AF: 0.552 AC: 1165 AN: 2112

Alfa AF: 0.554 Hom.: 23098

Bravo AF: 0.583

Asia WGS AF: 0.629 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.66
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs161981; hg19: chr12-32418251;