chr20-14331539-A-G

Variant names:

• chr20-14331539-A-G
• rs6110247
• NM_198391.3:c.-246-2212T>C

Variant summary

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

The NM_198391.3(FLRT3):​c.-246-2212T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,058 control chromosomes in the GnomAD database, including 2,583 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 0.16 (2583 hom., cov: 32)
• Consequence: FLRT3 NM_198391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910
• Publications: 3 publications found

Genes affected

FLRT3 (HGNC:3762): (fibronectin leucine rich transmembrane protein 3) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. FLRTs may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. This gene is expressed in many tissues. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2010]

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT3	NM_198391.3	c.-246-2212T>C		intron_variant	Intron 1 of 2	ENST00000341420.5	NP_938205.1
MACROD2	NM_001351661.2	c.272-161940A>G		intron_variant	Intron 3 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT3	ENST00000341420.5	c.-246-2212T>C		intron_variant	Intron 1 of 2	2	NM_198391.3	ENSP00000339912.4
MACROD2	ENST00000684519.1	c.272-161940A>G		intron_variant	Intron 3 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24841 AN: 151938 Hom.: 2583 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.163 AC: 24841 AN: 152058 Hom.: 2583 Cov.: 32 AF XY: 0.167 AC XY: 12444 AN XY: 74332

African (AFR) AF: 0.0410 AC: 1702 AN: 41534

American (AMR) AF: 0.153 AC: 2331 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1509 AN: 5154

South Asian (SAS) AF: 0.269 AC: 1300 AN: 4834

European-Finnish (FIN) AF: 0.248 AC: 2619 AN: 10574

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14037 AN: 67944

Other (OTH) AF: 0.184 AC: 388 AN: 2108

Alfa AF: 0.173 Hom.: 325

Bravo AF: 0.149

Asia WGS AF: 0.287 AC: 994 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6110247; hg19: chr20-14312185;