Variant 12-32216354-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001714.4(BICD1):c.321G>A(p.Gly107Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,614,202 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 102 hom. )

Consequence

BICD1
NM_001714.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00300

Variant links:

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]

BICD1 links:

BICD1 (HGNC:):

BICD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 12-32216354-G-A is Benign according to our data. Variant chr12-32216354-G-A is described in ClinVar as [Benign]. Clinvar id is 778588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.003 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00924 (13502/1461886) while in subpopulation MID AF= 0.034 (196/5768). AF 95% confidence interval is 0.0301. There are 102 homozygotes in gnomad4_exome. There are 6652 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD1	NM_001714.4 linkuse as main transcript	c.321G>A	p.Gly107Gly	synonymous_variant	2/10	ENST00000652176.1	NP_001705.2	Q96G01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BICD1	ENST00000652176.1 linkuse as main transcript	c.321G>A	p.Gly107Gly	synonymous_variant	2/10		NM_001714.4	ENSP00000498700.1	Q96G01-1
BICD1	ENST00000548411.6 linkuse as main transcript	c.321G>A	p.Gly107Gly	synonymous_variant	2/9	1		ENSP00000446793.1	Q96G01-4
BICD1	ENST00000395758.3 linkuse as main transcript	n.321G>A		non_coding_transcript_exon_variant	2/10	1		ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes

AF:

0.00804

AC:

1223

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00846

AC:

2128

AN:

251462

Hom.:

AF XY:

0.00898

AC XY:

1220

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00983

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00660

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.00924

AC:

13502

AN:

1461886

Hom.:

102

Cov.:

AF XY:

0.00915

AC XY:

6652

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00625

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.00980

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00802

AC:

1222

AN:

152316

Hom.:

Cov.:

AF XY:

0.00789

AC XY:

588

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00869

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0133

EpiControl

AF:

0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.5

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over