12-32216297-G-A

Variant names:

• chr12-32216297-G-A
• rs200761672
• NM_001714.4:c.264G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001714.4(BICD1):​c.264G>A​(p.Glu88Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000103 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: BICD1 NM_001714.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

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.264G>A	p.Glu88Glu	synonymous	Exon 2 of 10	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.264G>A	p.Glu88Glu	synonymous	Exon 2 of 9	NP_001400085.1
	BICD1	NM_001413157.1		c.264G>A	p.Glu88Glu	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.264G>A	p.Glu88Glu	synonymous	Exon 2 of 10	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.264G>A	p.Glu88Glu	synonymous	Exon 2 of 9	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.264G>A		non_coding_transcript_exon	Exon 2 of 10	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251470 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461812 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		5.3

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: rs200761672; hg19: chr12-32369231;