rs17594273

Variant names:

• chr17-60905232-A-G
• rs17594273
• NM_017679.5:c.822+2529A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017679.5(BCAS3):​c.822+2529A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 152,278 control chromosomes in the GnomAD database, including 83 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 0.029 (83 hom., cov: 32)
• Consequence: BCAS3 NM_017679.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• Publications: 2 publications found

Genes affected

BCAS3 (HGNC:14347): (BCAS3 microtubule associated cell migration factor) Enables several functions, including acetyltransferase activator activity; beta-tubulin binding activity; and histone acetyltransferase binding activity. Involved in cellular response to estrogen stimulus; positive regulation of catalytic activity; and positive regulation of transcription by RNA polymerase II. Located in nucleus; phagophore assembly site; and transcriptionally active chromatin. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

BCAS3 Gene-Disease associations (from GenCC):

• Hengel-Maroofian-Schols syndrome

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0286 (4349/152278) while in subpopulation NFE AF = 0.0441 (3001/67998). AF 95% confidence interval is 0.0428. There are 83 homozygotes in GnomAd4. There are 2061 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 83 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS3	NM_017679.5	c.822+2529A>G		intron_variant	Intron 11 of 23	ENST00000407086.8	NP_060149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8	c.822+2529A>G		intron_variant	Intron 11 of 23	1	NM_017679.5	ENSP00000385323.2

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4349 AN: 152160 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00704

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0286 AC: 4349 AN: 152278 Hom.: 83 Cov.: 32 AF XY: 0.0277 AC XY: 2061 AN XY: 74462

African (AFR) AF: 0.00702 AC: 292 AN: 41582

American (AMR) AF: 0.0196 AC: 300 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3466

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4830

European-Finnish (FIN) AF: 0.0416 AC: 441 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 3001 AN: 67998

Other (OTH) AF: 0.0280 AC: 59 AN: 2110

Alfa AF: 0.0400 Hom.: 281

Bravo AF: 0.0243

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.39
PhyloP100		0.70
Mutation Taster		=100/0	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: rs17594273; hg19: chr17-58982593;