rs2668301

Variant names:

• chr12-32142982-T-C
• rs2668301
• NM_001714.4:c.213+35438T>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.213+35438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,238 control chromosomes in the GnomAD database, including 2,550 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 0.18 (2550 hom., cov: 32)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.213+35438T>C		intron_variant	Intron 1 of 9	ENST00000652176.1	NP_001705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD1	ENST00000652176.1	c.213+35438T>C		intron_variant	Intron 1 of 9		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.213+35438T>C		intron_variant	Intron 1 of 8	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.213+35438T>C		intron_variant	Intron 1 of 9	1		ENSP00000379107.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27335 AN: 152120 Hom.: 2541 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.180 AC: 27366 AN: 152238 Hom.: 2550 Cov.: 32 AF XY: 0.174 AC XY: 12951 AN XY: 74442

African (AFR) AF: 0.212 AC: 8811 AN: 41526

American (AMR) AF: 0.110 AC: 1686 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5186

South Asian (SAS) AF: 0.154 AC: 742 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12611 AN: 68008

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.182 Hom.: 4862

Bravo AF: 0.179

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.49
PhyloP100		0.28
Mutation Taster		=97/3	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: rs2668301; hg19: chr12-32295916;