rs10844154

chr12-32227567-A-Cchr12-32227567-A-Gchr12-32227567-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001714.4(BICD1):c.426+11108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 153,330 control chromosomes in the GnomAD database, including 23,797 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 0.55 (23585 hom., cov: 32)
  • Exomes 𝑓: 0.55 (212 hom.)
• Consequence: BICD1 NM_001714.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD1	NM_001714.4	c.426+11108A>C		intron_variant		ENST00000652176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD1	ENST00000652176.1	c.426+11108A>C		intron_variant			NM_001714.4	A1
BICD1	ENST00000548411.6	c.426+11108A>C		intron_variant		1		P4
	ENST00000549976.1	n.588T>G		non_coding_transcript_exon_variant	1/1
BICD1	ENST00000395758.3	c.426+11108A>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83077 AN: 151950 Hom.: 23565 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.552 AC: 696 AN: 1262 Hom.: 212 Cov.: 0 AF XY: 0.523 AC XY: 343 AN XY: 656

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.547 AC: 83136 AN: 152068 Hom.: 23585 Cov.: 32 AF XY: 0.553 AC XY: 41126 AN XY: 74336

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.556

Alfa AF: 0.568 Hom.: 57274

Bravo AF: 0.546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.5
Dann	Benign	0.75

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: rs10844154; hg19: chr12-32380501;