17-61209283-G-C

Variant names:

• chr17-61209283-G-C
• rs8068952
• NM_017679.5:c.2425+124719G>C

Variant summary

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

The NM_017679.5(BCAS3):​c.2425+124719G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,660 control chromosomes in the GnomAD database, including 33,824 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 0.61 (33824 hom., cov: 32)
• Consequence: BCAS3 NM_017679.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 32 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017679.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS3	NM_017679.5	MANE Select	c.2425+124719G>C		intron	N/A	NP_060149.3
	BCAS3	NM_001353144.2		c.2560+124719G>C		intron	N/A	NP_001340073.1
	BCAS3	NM_001330413.2		c.2470+124719G>C		intron	N/A	NP_001317342.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS3	ENST00000407086.8	TSL:1 MANE Select	c.2425+124719G>C		intron	N/A	ENSP00000385323.2
	BCAS3	ENST00000390652.9	TSL:1	c.2470+124719G>C		intron	N/A	ENSP00000375067.4
	BCAS3	ENST00000589222.5	TSL:1	c.2425+124719G>C		intron	N/A	ENSP00000466078.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92733 AN: 151542 Hom.: 33814 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.612 AC: 92745 AN: 151660 Hom.: 33824 Cov.: 32 AF XY: 0.620 AC XY: 45940 AN XY: 74136

African (AFR) AF: 0.179 AC: 7351 AN: 41142

American (AMR) AF: 0.759 AC: 11582 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2319 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4560 AN: 5176

South Asian (SAS) AF: 0.851 AC: 4078 AN: 4790

European-Finnish (FIN) AF: 0.774 AC: 8160 AN: 10544

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52395 AN: 67960

Other (OTH) AF: 0.641 AC: 1351 AN: 2108

Alfa AF: 0.670 Hom.: 4695

Bravo AF: 0.589

Asia WGS AF: 0.770 AC: 2678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.50
PhyloP100		3.5
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: rs8068952; hg19: chr17-59286644;