rs10896

Variant names:

• chr19-19177119-A-G
• rs10896
• NM_001145784.2:c.*384T>C

Variant summary

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

The NM_001145784.2(BORCS8):​c.*384T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,852 control chromosomes in the GnomAD database, including 8,957 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 0.34 (8954 hom., cov: 30)
  • Exomes 𝑓: 0.43 (3 hom.)
• Consequence: BORCS8 NM_001145784.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83
• Publications: 17 publications found

Genes affected

BORCS8 (HGNC:37247): (BLOC-1 related complex subunit 8) Involved in heart development. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]

BORCS8-MEF2B (HGNC:39979): (BORCS8-MEF2B readthrough) This gene represents numerous read-through transcripts that span GeneID:729991 and 100271849. Many read-through transcripts are predicted to be nonsense-mediated decay (NMD) candidates, and are thought to be non-coding. Some transcripts are predicted to be capable of translation reinitiation at a downstream AUG, resulting in expression of at least one isoform of myocyte enhancer factor 2B (MEF2B) from this read-through locus. At least one additional MEF2B variant and isoform can be expressed from a downstream promoter, and is annotated on GeneID:100271849. [provided by RefSeq, Oct 2010]

MEF2B (HGNC:6995): (myocyte enhancer factor 2B) The product of this gene is a member of the MADS/MEF2 family of DNA binding proteins. The protein is thought to regulate gene expression, including expression of the smooth muscle myosin heavy chain gene. This region undergoes considerable alternative splicing, with transcripts supporting two non-overlapping loci (GeneID 729991 and 100271849) as well as numerous read-through transcripts that span both loci (annotated as GeneID 4207). Several isoforms of this protein are expressed from either this locus or from some of the read-through transcripts annotated on GeneID 4207. [provided by RefSeq, Jan 2014]

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 (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BORCS8	NM_001145784.2	c.*384T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000462790.8	NP_001139256.1
BORCS8-MEF2B	NM_005919.4	c.-30+3567T>C		intron_variant	Intron 3 of 9		NP_005910.1
BORCS8-MEF2B	NR_027307.2	n.437+3567T>C		intron_variant	Intron 5 of 12
BORCS8-MEF2B	NR_027308.2	n.437+3567T>C		intron_variant	Intron 5 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BORCS8	ENST00000462790.8	c.*384T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_001145784.2	ENSP00000425864.1
BORCS8-MEF2B	ENST00000514819.7	c.22+5454T>C		intron_variant	Intron 2 of 8	5		ENSP00000454967.3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50842 AN: 151704 Hom.: 8948 Cov.: 30

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.433 AC: 13 AN: 30 Hom.: 3 Cov.: 0 AF XY: 0.400 AC XY: 8 AN XY: 20

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 11 AN: 22

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.335 AC: 50863 AN: 151822 Hom.: 8954 Cov.: 30 AF XY: 0.334 AC XY: 24780 AN XY: 74166

African (AFR) AF: 0.245 AC: 10144 AN: 41416

American (AMR) AF: 0.373 AC: 5691 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1044 AN: 5128

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4820

European-Finnish (FIN) AF: 0.410 AC: 4307 AN: 10514

Middle Eastern (MID) AF: 0.293 AC: 85 AN: 290

European-Non Finnish (NFE) AF: 0.386 AC: 26232 AN: 67936

Other (OTH) AF: 0.317 AC: 667 AN: 2104

Alfa AF: 0.363 Hom.: 28965

Bravo AF: 0.328

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.5
DANN	Benign	0.44
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 17

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

Other links and lift over

dbSNP: rs10896; hg19: chr19-19287928;