12-32216354-G-A

Variant names:

• chr12-32216354-G-A
• rs144919300
• NM_001714.4:c.321G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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 (★★). Synonymous variant affecting the same amino acid position (i.e. G107G) has been classified as Uncertain significance.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00300
• Publications: 7 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 -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 6652 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	NM_001714.4	MANE Select	c.321G>A	p.Gly107Gly	synonymous	Exon 2 of 10	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.321G>A	p.Gly107Gly	synonymous	Exon 2 of 9	NP_001400085.1
	BICD1	NM_001413157.1		c.321G>A	p.Gly107Gly	synonymous	Exon 2 of 10	NP_001400086.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	ENST00000652176.1	MANE Select	c.321G>A	p.Gly107Gly	synonymous	Exon 2 of 10	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.321G>A	p.Gly107Gly	synonymous	Exon 2 of 9	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.321G>A		non_coding_transcript_exon	Exon 2 of 10	ENSP00000379107.3	A8MVZ6

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

GnomAD2 exomes AF: 0.00846 AC: 2128 AN: 251462 AF XY: 0.00898

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 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

African (AFR) AF: 0.00284 AC: 95 AN: 33480

American (AMR) AF: 0.0107 AC: 478 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0203 AC: 531 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00625 AC: 539 AN: 86258

European-Finnish (FIN) AF: 0.00240 AC: 128 AN: 53420

Middle Eastern (MID) AF: 0.0340 AC: 196 AN: 5768

European-Non Finnish (NFE) AF: 0.00980 AC: 10901 AN: 1112006

Other (OTH) AF: 0.0105 AC: 634 AN: 60394

GnomAD4 genome AF: 0.00802 AC: 1222 AN: 152316 Hom.: 5 Cov.: 32 AF XY: 0.00789 AC XY: 588 AN XY: 74484

African (AFR) AF: 0.00200 AC: 83 AN: 41568

American (AMR) AF: 0.0154 AC: 236 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4818

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 738 AN: 68034

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.5
DANN	Benign	0.64
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism

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: rs144919300; hg19: chr12-32369288;