rs35364034

Variant names:

• chr20-11923006-G-A
• rs35364034
• NM_014962.4:c.909G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-11923006-G-A
• chr20-11923006-G-T

Variant summary

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

The NM_014962.4(BTBD3):​c.909G>A​(p.Ala303Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,614,150 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (369 hom., cov: 33)
  • Exomes 𝑓: 0.057 (3674 hom.)
• Consequence: BTBD3 NM_014962.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.908
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 20-11923006-G-A is Benign according to our data. Variant chr20-11923006-G-A is described in ClinVar as Benign. ClinVar VariationId is 1226908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.908 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014962.4. 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
	BTBD3	NM_014962.4	MANE Select	c.909G>A	p.Ala303Ala	synonymous	Exon 4 of 4	NP_055777.1	Q9Y2F9-1
	BTBD3	NM_001395005.1		c.909G>A	p.Ala303Ala	synonymous	Exon 5 of 5	NP_001381934.1	Q9Y2F9-1
	BTBD3	NM_001395006.1		c.909G>A	p.Ala303Ala	synonymous	Exon 5 of 5	NP_001381935.1	Q9Y2F9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD3	ENST00000378226.7	TSL:1 MANE Select	c.909G>A	p.Ala303Ala	synonymous	Exon 4 of 4	ENSP00000367471.2	Q9Y2F9-1
	BTBD3	ENST00000618296.4	TSL:1	c.726G>A	p.Ala242Ala	synonymous	Exon 5 of 5	ENSP00000477589.1	Q9Y2F9-2
	BTBD3	ENST00000405977.5	TSL:5	c.909G>A	p.Ala303Ala	synonymous	Exon 5 of 5	ENSP00000384545.1	Q9Y2F9-1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8193 AN: 152192 Hom.: 373 Cov.: 33

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0540

GnomAD2 exomes AF: 0.0734 AC: 18322 AN: 249728 AF XY: 0.0740

Gnomad AFR exome AF: 0.0413

Gnomad AMR exome AF: 0.0845

Gnomad ASJ exome AF: 0.0528

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0472

Gnomad OTH exome AF: 0.0648

GnomAD4 exome AF: 0.0573 AC: 83738 AN: 1461840 Hom.: 3674 Cov.: 31 AF XY: 0.0593 AC XY: 43094 AN XY: 727216

African (AFR) AF: 0.0377 AC: 1261 AN: 33480

American (AMR) AF: 0.0818 AC: 3660 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 1321 AN: 26136

East Asian (EAS) AF: 0.253 AC: 10035 AN: 39700

South Asian (SAS) AF: 0.111 AC: 9549 AN: 86258

European-Finnish (FIN) AF: 0.0217 AC: 1157 AN: 53368

Middle Eastern (MID) AF: 0.0742 AC: 428 AN: 5768

European-Non Finnish (NFE) AF: 0.0472 AC: 52462 AN: 1112010

Other (OTH) AF: 0.0640 AC: 3865 AN: 60396

GnomAD4 genome AF: 0.0538 AC: 8193 AN: 152310 Hom.: 369 Cov.: 33 AF XY: 0.0548 AC XY: 4081 AN XY: 74488

African (AFR) AF: 0.0385 AC: 1601 AN: 41550

American (AMR) AF: 0.0637 AC: 975 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1335 AN: 5178

South Asian (SAS) AF: 0.120 AC: 579 AN: 4832

European-Finnish (FIN) AF: 0.0181 AC: 192 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3227 AN: 68030

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0442 Hom.: 153

Bravo AF: 0.0580

Asia WGS AF: 0.165 AC: 575 AN: 3478

EpiCase AF: 0.0526

EpiControl AF: 0.0511

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.86
PhyloP100		-0.91
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: rs35364034; hg19: chr20-11903654; COSMIC: COSV54778450; COSMIC: COSV54778450;