17-60945034-A-G

Variant names:

• chr17-60945034-A-G
• rs9914370
• NM_017679.5:c.1088-2185A>G

Variant summary

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

The NM_017679.5(BCAS3):​c.1088-2185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,038 control chromosomes in the GnomAD database, including 3,276 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 0.19 (3276 hom., cov: 32)
• Consequence: BCAS3 NM_017679.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 6 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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS3	NM_017679.5	c.1088-2185A>G		intron_variant	Intron 13 of 23	ENST00000407086.8	NP_060149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8	c.1088-2185A>G		intron_variant	Intron 13 of 23	1	NM_017679.5	ENSP00000385323.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29515 AN: 151920 Hom.: 3267 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.194 AC: 29545 AN: 152038 Hom.: 3276 Cov.: 32 AF XY: 0.191 AC XY: 14190 AN XY: 74334

African (AFR) AF: 0.315 AC: 13037 AN: 41436

American (AMR) AF: 0.171 AC: 2609 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3468

East Asian (EAS) AF: 0.134 AC: 689 AN: 5160

South Asian (SAS) AF: 0.0507 AC: 245 AN: 4828

European-Finnish (FIN) AF: 0.140 AC: 1481 AN: 10572

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10328 AN: 67986

Other (OTH) AF: 0.197 AC: 417 AN: 2116

Alfa AF: 0.167 Hom.: 10299

Bravo AF: 0.207

Asia WGS AF: 0.123 AC: 427 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.33
PhyloP100		-0.15
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: rs9914370; hg19: chr17-59022395; COSMIC: COSV66777308;