19-19180734-T-C

Variant names:

• chr19-19180734-T-C
• rs150355028
• NM_001145784.2:c.354A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001145784.2(BORCS8):​c.354A>G​(p.Ser118Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,550,506 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (20 hom.)
• Consequence: BORCS8 NM_001145784.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005402863).
• BP6: Variant 19-19180734-T-C is Benign according to our data. Variant chr19-19180734-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3777826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145784.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS8	NM_001145784.2	MANE Select	c.354A>G	p.Ser118Ser	synonymous	Exon 5 of 6	NP_001139256.1	Q96FH0-1
	BORCS8-MEF2B	NM_005919.4		c.-78A>G		5_prime_UTR	Exon 3 of 10	NP_005910.1
	BORCS8-MEF2B	NR_027307.2		n.389A>G		non_coding_transcript_exon	Exon 5 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BORCS8	ENST00000462790.8	TSL:1 MANE Select	c.354A>G	p.Ser118Ser	synonymous	Exon 5 of 6	ENSP00000425864.1	Q96FH0-1
	BORCS8-MEF2B	ENST00000514819.7	TSL:5	c.22+1839A>G		intron	N/A	ENSP00000454967.3	H3BNR1
	BORCS8	ENST00000585679.1	TSL:3	c.50A>G	p.Gln17Arg	missense	Exon 3 of 4	ENSP00000475370.1	U3KPZ4

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 357 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00438

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00191 AC: 284 AN: 149000 AF XY: 0.00195

Gnomad AFR exome AF: 0.000401

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.00108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.00432

Gnomad OTH exome AF: 0.00236

GnomAD4 exome AF: 0.00404 AC: 5647 AN: 1398252 Hom.: 20 Cov.: 30 AF XY: 0.00385 AC XY: 2653 AN XY: 689626

African (AFR) AF: 0.000697 AC: 22 AN: 31572

American (AMR) AF: 0.000281 AC: 10 AN: 35592

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 28 AN: 25152

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35724

South Asian (SAS) AF: 0.0000506 AC: 4 AN: 79114

European-Finnish (FIN) AF: 0.00189 AC: 93 AN: 49208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5284

European-Non Finnish (NFE) AF: 0.00494 AC: 5332 AN: 1078702

Other (OTH) AF: 0.00271 AC: 157 AN: 57904

GnomAD4 genome AF: 0.00234 AC: 357 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.00222 AC XY: 165 AN XY: 74444

African (AFR) AF: 0.000890 AC: 37 AN: 41572

American (AMR) AF: 0.000327 AC: 5 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000943 AC: 10 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00438 AC: 298 AN: 68000

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00347 Hom.: 3

Bravo AF: 0.00213

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00701 AC: 27

ExAC AF: 0.00130 AC: 34

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.0
DANN	Benign	0.82
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.0054	T
PhyloP100		-1.4
Vest4		0.094
MVP		0.25
GERP RS		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs150355028; hg19: chr19-19291543;