12-32216354-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001714.4(BICD1):c.321G>A(p.Gly107=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300

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 -15 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_single_submitter, 1 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 GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD1	NM_001714.4	c.321G>A	p.Gly107=	synonymous_variant	2/10	ENST00000652176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD1	ENST00000652176.1	c.321G>A	p.Gly107=	synonymous_variant	2/10		NM_001714.4	A1
BICD1	ENST00000548411.6	c.321G>A	p.Gly107=	synonymous_variant	2/9	1		P4
BICD1	ENST00000395758.3	c.321G>A	p.Gly107=	synonymous_variant, NMD_transcript_variant	2/10	1

Frequencies

GnomAD3 genomes AF: 0.00804 AC: 1223 AN: 152198 Hom.: 5 Cov.: 32

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.: 18 AF XY: 0.00898 AC XY: 1220 AN XY: 135902

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.: 31 AF XY: 0.00915 AC XY: 6652 AN XY: 727244

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.: 5 Cov.: 32 AF XY: 0.00789 AC XY: 588 AN XY: 74484

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.: 7

Bravo AF: 0.00869

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0133

EpiControl AF: 0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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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

Other links and lift over

dbSNP: rs144919300; hg19: chr12-32369288;