rs34447944

Variant names:

• chr12-32328435-C-T
• rs34447944
• NM_001714.4:c.1980C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001714.4(BICD1):​c.1980C>T​(p.Ala660Ala) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.950
• Publications: 9 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 -19 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 VariationId is 402426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.1980C>T	p.Ala660Ala	synonymous_variant	Exon 5 of 10	ENST00000652176.1	NP_001705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD1	ENST00000652176.1	c.1980C>T	p.Ala660Ala	synonymous_variant	Exon 5 of 10		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.1980C>T	p.Ala660Ala	synonymous_variant	Exon 5 of 9	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.1980C>T		non_coding_transcript_exon_variant	Exon 5 of 10	1		ENSP00000379107.3
BICD1	ENST00000547680.2	c.33C>T	p.Ala11Ala	synonymous_variant	Exon 1 of 2	3		ENSP00000475837.1

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

GnomAD2 exomes AF: 0.0744 AC: 18700 AN: 251186 AF XY: 0.0790

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 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

African (AFR) AF: 0.0126 AC: 422 AN: 33480

American (AMR) AF: 0.0471 AC: 2106 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3005 AN: 26132

East Asian (EAS) AF: 0.00904 AC: 359 AN: 39700

South Asian (SAS) AF: 0.126 AC: 10826 AN: 86250

European-Finnish (FIN) AF: 0.0774 AC: 4135 AN: 53418

Middle Eastern (MID) AF: 0.107 AC: 619 AN: 5768

European-Non Finnish (NFE) AF: 0.0843 AC: 93713 AN: 1111988

Other (OTH) AF: 0.0800 AC: 4832 AN: 60396

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

African (AFR) AF: 0.0146 AC: 607 AN: 41546

American (AMR) AF: 0.0586 AC: 897 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3472

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5176

South Asian (SAS) AF: 0.123 AC: 594 AN: 4820

European-Finnish (FIN) AF: 0.0745 AC: 789 AN: 10594

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0842 AC: 5729 AN: 68010

Other (OTH) AF: 0.0739 AC: 156 AN: 2110

Alfa AF: 0.0762 Hom.: 331

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	7.0
DANN	Benign	0.71
PhyloP100		-0.95
PromoterAI		-0.0036	Neutral
Mutation Taster		=100/0	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: rs34447944; hg19: chr12-32481369;