chr12-32353923-G-A

Position:

• chr12-32353923-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001714.4(BICD1):​c.2765-13747G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,922 control chromosomes in the GnomAD database, including 16,295 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 0.44 (16295 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD1	NM_001714.4	c.2765-13747G>A		intron_variant		ENST00000652176.1	NP_001705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICD1	ENST00000652176.1	c.2765-13747G>A		intron_variant			NM_001714.4	ENSP00000498700	A1
BICD1	ENST00000548411.6	c.2461-13747G>A		intron_variant		1		ENSP00000446793	P4
	ENST00000614539.1	n.1575G>A		non_coding_transcript_exon_variant	1/1
BICD1	ENST00000395758.3	c.*171-13747G>A		intron_variant, NMD_transcript_variant		1		ENSP00000379107

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67436 AN: 151804 Hom.: 16284 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.444

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.444 AC: 67484 AN: 151922 Hom.: 16295 Cov.: 31 AF XY: 0.447 AC XY: 33206 AN XY: 74252

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.446

Alfa AF: 0.502 Hom.: 26111

Bravo AF: 0.439

Asia WGS AF: 0.528 AC: 1833 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs155202; hg19: chr12-32506857;