12-32107615-CAAG-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001714.4(BICD1):c.213+75_213+77del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,462,370 control chromosomes in the GnomAD database, including 64 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (58 hom.)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-32107615-CAAG-C is Benign according to our data. Variant chr12-32107615-CAAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642834.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD1	NM_001714.4	c.213+75_213+77del		intron_variant		ENST00000652176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD1	ENST00000652176.1	c.213+75_213+77del		intron_variant			NM_001714.4	A1

Frequencies

GnomAD3 genomes AF: 0.00602 AC: 916 AN: 152142 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00764 AC: 1097 AN: 143658 Hom.: 11 AF XY: 0.00785 AC XY: 601 AN XY: 76588

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.0446

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00458

Gnomad FIN exome AF: 0.00326

Gnomad NFE exome AF: 0.00815

Gnomad OTH exome AF: 0.00770

GnomAD4 exome AF: 0.00755 AC: 9885 AN: 1310110 Hom.: 58 AF XY: 0.00758 AC XY: 4931 AN XY: 650800

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00340

Gnomad4 ASJ exome AF: 0.0465

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.00458

Gnomad4 FIN exome AF: 0.00417

Gnomad4 NFE exome AF: 0.00751

Gnomad4 OTH exome AF: 0.00832

GnomAD4 genome AF: 0.00601 AC: 915 AN: 152260 Hom.: 6 Cov.: 32 AF XY: 0.00575 AC XY: 428 AN XY: 74450

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00850

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0109 Hom.: 2

Bravo AF: 0.00573

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

BICD1: BS2 -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs541157159; hg19: chr12-32260549;