chr14-105249216-C-T

Variant names:

• chr14-105249216-C-T
• rs1187054017
• NM_001387567.1:c.434C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001387567.1(BTBD6):​c.434C>T​(p.Pro145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTBD6 NM_001387567.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.396
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079921186).
• BP6: Variant 14-105249216-C-T is Benign according to our data. Variant chr14-105249216-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3482806.Status of the report is criteria_provided_single_submitter, 1 stars.

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.434C>T	p.Pro145Leu	missense	Exon 2 of 4	NP_001374496.1	A0A8C8KHP4
	BRF1	NM_001519.4	MANE Select	c.544+3291G>A		intron	N/A	NP_001510.2
	BTBD6	NM_033271.3		c.275C>T	p.Pro92Leu	missense	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.434C>T	p.Pro145Leu	missense	Exon 2 of 4	ENSP00000376337.4	Q96KE9-3
	BRF1	ENST00000547530.7	TSL:1 MANE Select	c.544+3291G>A		intron	N/A	ENSP00000448387.2	Q92994-1
	BRF1	ENST00000379937.6	TSL:1	c.463+3291G>A		intron	N/A	ENSP00000369269.2	Q92994-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000969 AC: 2 AN: 206490 AF XY: 0.00000880

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435406 Hom.: 0 Cov.: 45 AF XY: 0.00000140 AC XY: 1 AN XY: 713310

African (AFR) AF: 0.00 AC: 0 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 43004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 39222

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105534

Other (OTH) AF: 0.00 AC: 0 AN: 59634

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000660 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.016	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.40
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.081
Sift	Benign	0.37	T
Sift4G	Benign	0.26	T
Polyphen		0.0090	B
Vest4		0.18
MutPred		0.33		Gain of stability (P = 0.0061)
MVP		0.30
MPC		0.40
ClinPred		0.026	T
GERP RS		-3.6
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.16
Mutation Taster		=88/12	polymorphism

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: rs1187054017; hg19: chr14-105715553;