NM_001714.4:c.426+31899A>G

Variant names:

• chr12-32248358-A-G
• rs326644
• NM_001714.4:c.426+31899A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001714.4(BICD1):​c.426+31899A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,010 control chromosomes in the GnomAD database, including 14,228 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 0.43 (14228 hom., cov: 31)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD1	NM_001714.4	c.426+31899A>G		intron_variant	Intron 2 of 9	ENST00000652176.1	NP_001705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD1	ENST00000652176.1	c.426+31899A>G		intron_variant	Intron 2 of 9		NM_001714.4	ENSP00000498700.1
BICD1	ENST00000548411.6	c.426+31899A>G		intron_variant	Intron 2 of 8	1		ENSP00000446793.1
BICD1	ENST00000395758.3	n.426+31899A>G		intron_variant	Intron 2 of 9	1		ENSP00000379107.3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65279 AN: 151892 Hom.: 14225 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 65316 AN: 152010 Hom.: 14228 Cov.: 31 AF XY: 0.425 AC XY: 31608 AN XY: 74304

African (AFR) AF: 0.387 AC: 16057 AN: 41460

American (AMR) AF: 0.364 AC: 5559 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1652 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2133 AN: 5152

South Asian (SAS) AF: 0.422 AC: 2033 AN: 4820

European-Finnish (FIN) AF: 0.428 AC: 4511 AN: 10548

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32016 AN: 67958

Other (OTH) AF: 0.415 AC: 875 AN: 2106

Alfa AF: 0.456 Hom.: 68764

Bravo AF: 0.419

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.89
PhyloP100		-0.56
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

Other links and lift over

dbSNP: rs326644; hg19: chr12-32401292;