chr6-42828818-C-G

Variant names:

• chr6-42828818-C-G
• rs1249165374
• NM_001393499.1:c.485C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001393499.1(BICRAL):​c.485C>G​(p.Thr162Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T162M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BICRAL NM_001393499.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393499.1. 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
	BICRAL	NM_001393499.1	MANE Select	c.485C>G	p.Thr162Arg	missense	Exon 6 of 13	NP_001380428.1	Q6AI39
	BICRAL	NM_001318819.2		c.485C>G	p.Thr162Arg	missense	Exon 7 of 14	NP_001305748.1	Q6AI39
	BICRAL	NM_015349.3		c.485C>G	p.Thr162Arg	missense	Exon 5 of 12	NP_056164.1	Q6AI39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICRAL	ENST00000314073.10	TSL:1 MANE Select	c.485C>G	p.Thr162Arg	missense	Exon 6 of 13	ENSP00000313933.4	Q6AI39
	BICRAL	ENST00000394168.1	TSL:1	c.485C>G	p.Thr162Arg	missense	Exon 5 of 12	ENSP00000377723.1	Q6AI39
	BICRAL	ENST00000909955.1		c.485C>G	p.Thr162Arg	missense	Exon 5 of 12	ENSP00000580014.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727238

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.89	T
PhyloP100		5.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.49		Loss of glycosylation at T162 (P = 0.0394)
MVP		0.043
MPC		0.77
ClinPred		0.82	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.70
Mutation Taster		=74/26	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: rs1249165374; hg19: chr6-42796556;