6-42829042-A-G

Variant names:

• chr6-42829042-A-G
• NM_001393499.1:c.709A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393499.1(BICRAL):​c.709A>G​(p.Ile237Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,810 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BICRAL NM_001393499.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1870977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICRAL	NM_001393499.1	c.709A>G	p.Ile237Val	missense_variant	Exon 6 of 13	ENST00000314073.10	NP_001380428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICRAL	ENST00000314073.10	c.709A>G	p.Ile237Val	missense_variant	Exon 6 of 13	1	NM_001393499.1	ENSP00000313933.4
BICRAL	ENST00000394168.1	c.709A>G	p.Ile237Val	missense_variant	Exon 5 of 12	1		ENSP00000377723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.709A>G (p.I237V) alteration is located in exon 5 (coding exon 4) of the GLTSCR1L gene. This alteration results from a A to G substitution at nucleotide position 709, causing the isoleucine (I) at amino acid position 237 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;.;.
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.25	.;N;N
REVEL	Benign	0.12
Sift	Benign	0.24	.;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.76	P;P;P
Vest4		0.20
MutPred		0.27		Loss of methylation at K239 (P = 0.1113);Loss of methylation at K239 (P = 0.1113);Loss of methylation at K239 (P = 0.1113);
MVP		0.043
MPC		0.72
ClinPred		0.66	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.22

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42796780;