NM_001714.4:c.1704G>C

Variant names:

• chr12-32328159-G-C
• rs3748275
• NM_001714.4:c.1704G>C
• BICD1 p.Val568Val

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001714.4(BICD1):​c.1704G>C​(p.Val568Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,888 control chromosomes in the GnomAD database, including 45,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4157 hom., cov: 31)
  • Exomes 𝑓: 0.22 (41024 hom.)
• Consequence: BICD1 NM_001714.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.847
• Publications: 12 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 12-32328159-G-C is Benign according to our data. Variant chr12-32328159-G-C is described in ClinVar as Benign. ClinVar VariationId is 402425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.847 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	NM_001714.4	MANE Select	c.1704G>C	p.Val568Val	synonymous	Exon 5 of 10	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.1704G>C	p.Val568Val	synonymous	Exon 5 of 9	NP_001400085.1
	BICD1	NM_001413157.1		c.1704G>C	p.Val568Val	synonymous	Exon 5 of 10	NP_001400086.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	ENST00000652176.1	MANE Select	c.1704G>C	p.Val568Val	synonymous	Exon 5 of 10	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.1704G>C	p.Val568Val	synonymous	Exon 5 of 9	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.1704G>C		non_coding_transcript_exon	Exon 5 of 10	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33038 AN: 151922 Hom.: 4150 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.238 AC: 59742 AN: 251248 AF XY: 0.235

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.224 AC: 326850 AN: 1461848 Hom.: 41024 Cov.: 35 AF XY: 0.222 AC XY: 161129 AN XY: 727228

African (AFR) AF: 0.154 AC: 5140 AN: 33478

American (AMR) AF: 0.193 AC: 8620 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4234 AN: 26136

East Asian (EAS) AF: 0.653 AC: 25921 AN: 39696

South Asian (SAS) AF: 0.170 AC: 14657 AN: 86254

European-Finnish (FIN) AF: 0.311 AC: 16622 AN: 53412

Middle Eastern (MID) AF: 0.108 AC: 622 AN: 5768

European-Non Finnish (NFE) AF: 0.214 AC: 237867 AN: 1111984

Other (OTH) AF: 0.218 AC: 13167 AN: 60396

GnomAD4 genome AF: 0.218 AC: 33078 AN: 152040 Hom.: 4157 Cov.: 31 AF XY: 0.224 AC XY: 16657 AN XY: 74282

African (AFR) AF: 0.152 AC: 6327 AN: 41508

American (AMR) AF: 0.207 AC: 3167 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3072 AN: 5142

South Asian (SAS) AF: 0.185 AC: 889 AN: 4818

European-Finnish (FIN) AF: 0.322 AC: 3398 AN: 10554

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14989 AN: 67948

Other (OTH) AF: 0.217 AC: 459 AN: 2114

Alfa AF: 0.216 Hom.: 1196

Bravo AF: 0.210

Asia WGS AF: 0.327 AC: 1136 AN: 3478

EpiCase AF: 0.211

EpiControl AF: 0.203

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.2
DANN	Benign	0.69
PhyloP100		0.85
PromoterAI		-0.0093	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3748275;

hg19: chr12-32481093;

COSMIC: COSV55675939;

COSMIC: COSV55675939;