rs1381246

Variant names:

• chr11-122978266-C-G
• rs1381246
• NM_001098169.2:c.460-375G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098169.2(BSX):​c.460-375G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,002 control chromosomes in the GnomAD database, including 21,882 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21882 hom., cov: 32)
• Consequence: BSX NM_001098169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 3 publications found

Genes affected

BSX (HGNC:20450): (brain specific homeobox) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including eating behavior; mammary gland involution; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSX	NM_001098169.2	c.460-375G>C		intron_variant	Intron 2 of 2	ENST00000343035.3	NP_001091639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSX	ENST00000343035.3	c.460-375G>C		intron_variant	Intron 2 of 2	5	NM_001098169.2	ENSP00000344285.2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79729 AN: 151884 Hom.: 21835 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.525 AC: 79826 AN: 152002 Hom.: 21882 Cov.: 32 AF XY: 0.520 AC XY: 38632 AN XY: 74286

African (AFR) AF: 0.695 AC: 28825 AN: 41456

American (AMR) AF: 0.374 AC: 5703 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2420 AN: 5172

South Asian (SAS) AF: 0.435 AC: 2093 AN: 4810

European-Finnish (FIN) AF: 0.515 AC: 5434 AN: 10542

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32117 AN: 67976

Other (OTH) AF: 0.493 AC: 1041 AN: 2112

Alfa AF: 0.508 Hom.: 2535

Bravo AF: 0.523

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs1381246; hg19: chr11-122848974;