Genetic Variant BICD1:c.426+11108A>C (chr12-32227567-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001714.4(BICD1):c.426+11108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 153,330 control chromosomes in the GnomAD database, including 23,797 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 0.55 ( 23585 hom., cov: 32)

Exomes 𝑓: 0.55 ( 212 hom. )

Consequence

BICD1
NM_001714.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

18 publications found

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:

ENSG00000258134 (HGNC:):

ENSG00000258134 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BICD1	NM_001714.4	MANE Select	c.426+11108A>C	intron	N/A	NP_001705.2	Q96G01-1
BICD1	NM_001413156.1		c.426+11108A>C	intron	N/A	NP_001400085.1
BICD1	NM_001413157.1		c.426+11108A>C	intron	N/A	NP_001400086.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BICD1	ENST00000652176.1	MANE Select	c.426+11108A>C	intron	N/A	ENSP00000498700.1	Q96G01-1
BICD1	ENST00000548411.6	TSL:1	c.426+11108A>C	intron	N/A	ENSP00000446793.1	Q96G01-4
BICD1	ENST00000395758.3	TSL:1	n.426+11108A>C	intron	N/A	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83077

AN:

151950

Hom.:

23565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.867

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.561

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.552

AC:

696

AN:

1262

Hom.:

212

Cov.:

AF XY:

0.523

AC XY:

343

AN XY:

656

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.647

AC:

101

AN:

156

European-Finnish (FIN)

AF:

0.536

AC:

509

AN:

950

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.545

AC:

AN:

112

Other (OTH)

AF:

0.611

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.547

AC:

83136

AN:

152068

Hom.:

23585

Cov.:

AF XY:

0.553

AC XY:

41126

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.424

AC:

17592

AN:

41470

American (AMR)

AF:

0.651

AC:

9958

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1772

AN:

3472

East Asian (EAS)

AF:

0.867

AC:

4480

AN:

5168

South Asian (SAS)

AF:

0.717

AC:

3456

AN:

4818

European-Finnish (FIN)

AF:

0.565

AC:

5983

AN:

10592

Middle Eastern (MID)

AF:

0.507

AC:

148

AN:

292

European-Non Finnish (NFE)

AF:

0.561

AC:

38152

AN:

67948

Other (OTH)

AF:

0.556

AC:

1174

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1881

3762

5642

7523

9404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.563

Hom.:

112138

Bravo

AF:

0.546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.5

(source)

DANN

Benign

0.75

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over