20-11920574-G-C

Variant names:

• chr20-11920574-G-C
• rs4814041
• NM_014962.4:c.536+738G>C

Variant summary

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

The NM_014962.4(BTBD3):​c.536+738G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,188 control chromosomes in the GnomAD database, including 47,442 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 0.79 (47442 hom., cov: 33)
• Consequence: BTBD3 NM_014962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 1 publications found

Genes affected

BTBD3 (HGNC:15854): (BTB domain containing 3) Enables identical protein binding activity. Predicted to be involved in cerebral cortex development and dendrite morphogenesis. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD3	NM_014962.4	c.536+738G>C		intron_variant	Intron 3 of 3	ENST00000378226.7	NP_055777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD3	ENST00000378226.7	c.536+738G>C		intron_variant	Intron 3 of 3	1	NM_014962.4	ENSP00000367471.2

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119662 AN: 152068 Hom.: 47430 Cov.: 33

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.787 AC: 119720 AN: 152188 Hom.: 47442 Cov.: 33 AF XY: 0.786 AC XY: 58507 AN XY: 74412

African (AFR) AF: 0.695 AC: 28832 AN: 41502

American (AMR) AF: 0.804 AC: 12289 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2726 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3898 AN: 5184

South Asian (SAS) AF: 0.759 AC: 3663 AN: 4828

European-Finnish (FIN) AF: 0.849 AC: 8998 AN: 10600

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56685 AN: 67998

Other (OTH) AF: 0.777 AC: 1638 AN: 2108

Alfa AF: 0.816 Hom.: 6314

Bravo AF: 0.779

Asia WGS AF: 0.737 AC: 2563 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.50
PhyloP100		0.0040
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: rs4814041; hg19: chr20-11901222;