rs193921035

chr6-42830111-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_001393499.1(BICRAL):c.1778A>G(p.Lys593Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: BICRAL NM_001393499.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.87

Genes affected

BICRAL (HGNC:21111): (BICRA like chromatin remodeling complex associated protein) Predicted to be involved in positive regulation of transcription, DNA-templated. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, BICRAL
• BP4: Computational evidence support a benign effect (MetaRNN=0.21611688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRAL	NM_001393499.1	c.1778A>G	p.Lys593Arg	missense_variant	6/13	ENST00000314073.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRAL	ENST00000314073.10	c.1778A>G	p.Lys593Arg	missense_variant	6/13	1	NM_001393499.1	P1
BICRAL	ENST00000394168.1	c.1778A>G	p.Lys593Arg	missense_variant	5/12	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461812 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;.;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.89	D;D;D
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.87	P;P;P
Vest4		0.46
MutPred		0.18		Loss of ubiquitination at K593 (P = 0.0047);Loss of ubiquitination at K593 (P = 0.0047);Loss of ubiquitination at K593 (P = 0.0047);
MVP		0.082
MPC		0.70
ClinPred		0.80	D
GERP RS		4.9
Varity_R		0.063
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193921035; hg19: chr6-42797849; COSMIC: COSV58405520;