rs261889

chr12-32327122-A-Gchr12-32327122-A-T

Variant summary

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

The NM_001714.4(BICD1):c.1006-339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,136 control chromosomes in the GnomAD database, including 51,676 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 0.82 (51676 hom., cov: 31)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD1	NM_001714.4	c.1006-339A>G		intron_variant		ENST00000652176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD1	ENST00000652176.1	c.1006-339A>G		intron_variant			NM_001714.4	A1
BICD1	ENST00000548411.6	c.1006-339A>G		intron_variant		1		P4
BICD1	ENST00000395758.3	c.1006-339A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125091 AN: 152018 Hom.: 51640 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.823 AC: 125179 AN: 152136 Hom.: 51676 Cov.: 31 AF XY: 0.820 AC XY: 60989 AN XY: 74382

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.822

Alfa AF: 0.826 Hom.: 7086

Bravo AF: 0.813

Asia WGS AF: 0.789 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	6.2
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs261889; hg19: chr12-32480056;