chr1-44813237-C-T

Variant names:

• chr1-44813237-C-T
• rs920910130
• NM_001136537.3:c.583C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136537.3(BTBD19):​c.583C>T​(p.Arg195Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000325 in 1,539,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R195H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: BTBD19 NM_001136537.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0650
• Publications: 0 publications found

Genes affected

BTBD19 (HGNC:27145): (BTB domain containing 19)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27425462).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136537.3. 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
	BTBD19	NM_001136537.3	MANE Select	c.583C>T	p.Arg195Cys	missense	Exon 6 of 8	NP_001130009.1	C9JJ37-1
	BTBD19	NM_001394561.1		c.844C>T	p.Arg282Cys	missense	Exon 5 of 7	NP_001381490.1
	BTBD19	NM_001394562.1		c.646C>T	p.Arg216Cys	missense	Exon 6 of 8	NP_001381491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD19	ENST00000450269.6	TSL:5 MANE Select	c.583C>T	p.Arg195Cys	missense	Exon 6 of 8	ENSP00000395461.1	C9JJ37-1
	BTBD19	ENST00000409335.6	TSL:5	c.469C>T	p.Arg157Cys	missense	Exon 4 of 6	ENSP00000386506.2	A0A0A0MSF5
	BTBD19	ENST00000718238.1		c.469C>T	p.Arg157Cys	missense	Exon 4 of 6	ENSP00000520683.1	A0A0A0MSF5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000284 AC: 4 AN: 140784 AF XY: 0.0000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000164

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: 0.00000288 AC: 4 AN: 1387174 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 683708

African (AFR) AF: 0.00 AC: 0 AN: 31428

American (AMR) AF: 0.000113 AC: 4 AN: 35426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25040

East Asian (EAS) AF: 0.00 AC: 0 AN: 35550

South Asian (SAS) AF: 0.00 AC: 0 AN: 79028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075770

Other (OTH) AF: 0.00 AC: 0 AN: 57658

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.065
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.14
Sift	Benign	0.043	D
Sift4G	Benign	0.14	T
Polyphen		0.88	P
Vest4		0.22
MutPred		0.43		Loss of MoRF binding (P = 0.0042)
MVP		0.17
ClinPred		0.31	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.23
Mutation Taster		=94/6	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: rs920910130; hg19: chr1-45278909;