chr19-19177119-A-G

Position:

• chr19-19177119-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
BORCS8	NM_001145784.2	c.*384T>C		3_prime_UTR_variant	6/6	ENST00000462790.8	NP_001139256.1
BORCS8-MEF2B	NR_027308.2	n.437+3567T>C		intron_variant, non_coding_transcript_variant
BORCS8-MEF2B	NM_005919.4	c.-30+3567T>C		intron_variant			NP_005910.1
BORCS8-MEF2B	NR_027307.2	n.437+3567T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BORCS8	ENST00000462790.8	c.*384T>C		3_prime_UTR_variant	6/6	1	NM_001145784.2	ENSP00000425864	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.317

Alfa AF: 0.370 Hom.: 17585

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10896; hg19: chr19-19287928;