20-50830276-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_198799.4(BCAS4):c.163-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,612,300 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (14 hom.)
• Consequence: BCAS4 NM_198799.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.3591
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.47

Genes affected

BCAS4 (HGNC:14367): (breast carcinoma amplified sequence 4) Predicted to be part of BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 20-50830276-C-T is Benign according to our data. Variant chr20-50830276-C-T is described in ClinVar as [Benign]. Clinvar id is 779192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAS4	NM_198799.4	c.163-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAS4	ENST00000371608.8	c.163-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_198799.4	P2

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152224 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00193 AC: 484 AN: 251046 Hom.: 4 AF XY: 0.00174 AC XY: 236 AN XY: 135674

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00296

Gnomad ASJ exome AF: 0.0286

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.000879 AC: 1284 AN: 1459958 Hom.: 14 Cov.: 30 AF XY: 0.000896 AC XY: 651 AN XY: 726454

Gnomad4 AFR exome AF: 0.000658

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000261

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152342 Hom.: 2 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74486

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00309 Hom.: 1

Bravo AF: 0.00166

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	16
Dann	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.36
dbscSNV1_RF	Benign	0.25
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs188902261; hg19: chr20-49446813; COSMIC: COSV52812872;