rs34447944

chr12-32328435-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001714.4(BICD1):c.1980C>T(p.Ala660=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,614,082 control chromosomes in the GnomAD database, including 5,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (414 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5536 hom.)
• Consequence: BICD1 NM_001714.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 12-32328435-C-T is Benign according to our data. Variant chr12-32328435-C-T is described in ClinVar as [Benign]. Clinvar id is 402426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD1	NM_001714.4	c.1980C>T	p.Ala660=	synonymous_variant	5/10	ENST00000652176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD1	ENST00000652176.1	c.1980C>T	p.Ala660=	synonymous_variant	5/10		NM_001714.4	A1
BICD1	ENST00000548411.6	c.1980C>T	p.Ala660=	synonymous_variant	5/9	1		P4
BICD1	ENST00000395758.3	c.1980C>T	p.Ala660=	synonymous_variant, NMD_transcript_variant	5/10	1
BICD1	ENST00000547680.2	c.36C>T	p.Ala12=	synonymous_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9411 AN: 152108 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.0747

GnomAD3 exomes AF: 0.0744 AC: 18700 AN: 251186 Hom.: 911 AF XY: 0.0790 AC XY: 10728 AN XY: 135784

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.0444

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00794

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.0778

Gnomad NFE exome AF: 0.0856

Gnomad OTH exome AF: 0.0865

GnomAD4 exome AF: 0.0821 AC: 120017 AN: 1461856 Hom.: 5536 Cov.: 35 AF XY: 0.0840 AC XY: 61077 AN XY: 727224

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0471

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.00904

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0774

Gnomad4 NFE exome AF: 0.0843

Gnomad4 OTH exome AF: 0.0800

GnomAD4 genome AF: 0.0618 AC: 9408 AN: 152226 Hom.: 414 Cov.: 32 AF XY: 0.0635 AC XY: 4727 AN XY: 74428

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0586

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0842

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0779 Hom.: 249

Bravo AF: 0.0577

Asia WGS AF: 0.0540 AC: 189 AN: 3478

EpiCase AF: 0.0898

EpiControl AF: 0.0928

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	7.0
Dann	Benign	0.71

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: rs34447944; hg19: chr12-32481369;