14-35928474-C-T

Variant names:

• chr14-35928474-C-T
• rs1168987
• ENST00000551774.1:c.597-3249C>T

Variant summary

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

The ENST00000551774.1(BRMS1L):​c.597-3249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,080 control chromosomes in the GnomAD database, including 950 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 0.10 (950 hom., cov: 32)
• Consequence: BRMS1L ENST00000551774.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 9 publications found

Genes affected

BRMS1L (HGNC:20512): (BRMS1 like transcriptional repressor) The protein encoded by this gene shows sequence similarity to the human breast carcinoma metastasis suppressor (BRMS1) protein and the mammalian Sds3 (suppressor of defective silencing 3) proteins. This protein is a component of the mSin3a family of histone deacetylase complexes (HDAC). [provided by RefSeq, Jul 2008]

LINC00609 (HGNC:43960): (long intergenic non-protein coding RNA 609)

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 (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRMS1L	ENST00000551774.1	c.597-3249C>T		intron_variant	Intron 7 of 7	1		ENSP00000446826.1
LINC00609	ENST00000550089.2	n.288+29634C>T		intron_variant	Intron 2 of 4	3
LINC00609	ENST00000660969.2	n.340+29634C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15904 AN: 151962 Hom.: 952 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.0978

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

GnomAD4 genome AF: 0.105 AC: 15914 AN: 152080 Hom.: 950 Cov.: 32 AF XY: 0.107 AC XY: 7919 AN XY: 74350

African (AFR) AF: 0.159 AC: 6599 AN: 41468

American (AMR) AF: 0.111 AC: 1703 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5162

South Asian (SAS) AF: 0.174 AC: 838 AN: 4814

European-Finnish (FIN) AF: 0.0483 AC: 511 AN: 10576

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4412 AN: 67996

Other (OTH) AF: 0.0968 AC: 204 AN: 2108

Alfa AF: 0.0833 Hom.: 1526

Bravo AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs1168987; hg19: chr14-36397680;