14-105249178-C-T

Variant names:

• chr14-105249178-C-T
• rs2816605
• NM_001387567.1:c.396C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001387567.1(BTBD6):​c.396C>T​(p.Asn132Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,581,986 control chromosomes in the GnomAD database, including 52,226 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 0.20 (3818 hom., cov: 33)
  • Exomes 𝑓: 0.26 (48408 hom.)
• Consequence: BTBD6 NM_001387567.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 23 publications found

Genes affected

BTBD6 (HGNC:19897): (BTB domain containing 6) Predicted to be involved in neurogenesis. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BRF1 (HGNC:11551): (BRF1 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Several alternatively spliced variants encoding different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. [provided by RefSeq, Jun 2011]

BRF1 Gene-Disease associations (from GenCC):

• cerebellar-facial-dental syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=0.653 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387567.1. 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
	BTBD6	NM_001387567.1	MANE Select	c.396C>T	p.Asn132Asn	synonymous	Exon 2 of 4	NP_001374496.1	A0A8C8KHP4
	BRF1	NM_001519.4	MANE Select	c.544+3329G>A		intron	N/A	NP_001510.2
	BTBD6	NM_033271.3		c.237C>T	p.Asn79Asn	synonymous	Exon 3 of 5	NP_150374.2	Q96KE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD6	ENST00000392554.8	TSL:1 MANE Select	c.396C>T	p.Asn132Asn	synonymous	Exon 2 of 4	ENSP00000376337.4	Q96KE9-3
	BRF1	ENST00000547530.7	TSL:1 MANE Select	c.544+3329G>A		intron	N/A	ENSP00000448387.2	Q92994-1
	BRF1	ENST00000379937.6	TSL:1	c.463+3329G>A		intron	N/A	ENSP00000369269.2	Q92994-5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30943 AN: 151964 Hom.: 3821 Cov.: 33

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.213 AC: 43303 AN: 203758 AF XY: 0.219

Gnomad AFR exome AF: 0.0651

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.256 AC: 366103 AN: 1429906 Hom.: 48408 Cov.: 49 AF XY: 0.256 AC XY: 181756 AN XY: 710004

African (AFR) AF: 0.0702 AC: 2337 AN: 33298

American (AMR) AF: 0.187 AC: 7951 AN: 42456

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5749 AN: 25676

East Asian (EAS) AF: 0.138 AC: 5414 AN: 39104

South Asian (SAS) AF: 0.234 AC: 19642 AN: 83906

European-Finnish (FIN) AF: 0.323 AC: 12039 AN: 37276

Middle Eastern (MID) AF: 0.269 AC: 1479 AN: 5490

European-Non Finnish (NFE) AF: 0.269 AC: 297301 AN: 1103218

Other (OTH) AF: 0.239 AC: 14191 AN: 59482

GnomAD4 genome AF: 0.203 AC: 30938 AN: 152080 Hom.: 3818 Cov.: 33 AF XY: 0.205 AC XY: 15255 AN XY: 74344

African (AFR) AF: 0.0775 AC: 3219 AN: 41548

American (AMR) AF: 0.176 AC: 2688 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3472

East Asian (EAS) AF: 0.126 AC: 647 AN: 5134

South Asian (SAS) AF: 0.230 AC: 1113 AN: 4830

European-Finnish (FIN) AF: 0.342 AC: 3607 AN: 10542

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18206 AN: 67938

Other (OTH) AF: 0.211 AC: 446 AN: 2116

Alfa AF: 0.238 Hom.: 4976

Bravo AF: 0.190

Asia WGS AF: 0.145 AC: 506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		0.65
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=98/2	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: rs2816605; hg19: chr14-105715515; COSMIC: COSV59273956; COSMIC: COSV59273956;