17-61286621-C-T

Variant names:

• chr17-61286621-C-T
• rs4968551
• NM_017679.5:c.2426-81706C>T

Variant summary

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

The NM_017679.5(BCAS3):​c.2426-81706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,036 control chromosomes in the GnomAD database, including 1,222 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 (1222 hom., cov: 32)
• Consequence: BCAS3 NM_017679.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 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.2426-81706C>T		intron	N/A	NP_060149.3
	BCAS3	NM_001353144.2		c.2561-81706C>T		intron	N/A	NP_001340073.1
	BCAS3	NM_001330413.2		c.2471-81706C>T		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.2426-81706C>T		intron	N/A	ENSP00000385323.2
	BCAS3	ENST00000390652.9	TSL:1	c.2471-81706C>T		intron	N/A	ENSP00000375067.4
	BCAS3	ENST00000589222.5	TSL:1	c.2426-81706C>T		intron	N/A	ENSP00000466078.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18982 AN: 151918 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.125 AC: 18990 AN: 152036 Hom.: 1222 Cov.: 32 AF XY: 0.123 AC XY: 9144 AN XY: 74316

African (AFR) AF: 0.128 AC: 5289 AN: 41448

American (AMR) AF: 0.103 AC: 1581 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3466

East Asian (EAS) AF: 0.107 AC: 551 AN: 5158

South Asian (SAS) AF: 0.198 AC: 952 AN: 4818

European-Finnish (FIN) AF: 0.0799 AC: 845 AN: 10574

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8586 AN: 67970

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.111 Hom.: 450

Bravo AF: 0.127

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-1.2
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: rs4968551; hg19: chr17-59363982;