17-60889177-T-C

Variant names:

• chr17-60889177-T-C
• rs7224438
• NM_017679.5:c.662-518T>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.662-518T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,228 control chromosomes in the GnomAD database, including 3,424 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 0.12 (3424 hom., cov: 32)
• Consequence: BCAS3 NM_017679.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 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.662-518T>C		intron	N/A	NP_060149.3
	BCAS3	NM_001353144.2		c.662-518T>C		intron	N/A	NP_001340073.1
	BCAS3	NM_001330413.2		c.662-518T>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.662-518T>C		intron	N/A	ENSP00000385323.2
	BCAS3	ENST00000390652.9	TSL:1	c.662-518T>C		intron	N/A	ENSP00000375067.4
	BCAS3	ENST00000589222.5	TSL:1	c.662-518T>C		intron	N/A	ENSP00000466078.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18458 AN: 152112 Hom.: 3400 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00428

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.122 AC: 18525 AN: 152228 Hom.: 3424 Cov.: 32 AF XY: 0.118 AC XY: 8764 AN XY: 74428

African (AFR) AF: 0.399 AC: 16559 AN: 41470

American (AMR) AF: 0.0555 AC: 849 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3466

East Asian (EAS) AF: 0.0914 AC: 474 AN: 5186

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4822

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10622

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.00426 AC: 290 AN: 68038

Other (OTH) AF: 0.0888 AC: 188 AN: 2116

Alfa AF: 0.0536 Hom.: 3757

Bravo AF: 0.138

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.56
PhyloP100		0.19
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: rs7224438; hg19: chr17-58966538;