Genetic Variant LOC102723321:n.82-4168C>T (chr1-147773393-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The XR_922079.4(LOC102723321):n.82-4168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,214 control chromosomes in the GnomAD database, including 3,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3159 hom., cov: 31)

Exomes 𝑓: 0.17 ( 6 hom. )

Consequence

LOC102723321
XR_922079.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

LOC102723321 (HGNC:):

LOC102723321 links:

GJA5 (HGNC:4279): (gap junction protein alpha 5) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene may be associated with atrial fibrillation. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008]

GJA5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102723321	XR_922079.4 link	n.82-4168C>T		intron_variant	Intron 1 of 2
GJA5	NM_005266.7 link	c.-175G>A		upstream_gene_variant			NP_005257.2	P36382X5D2H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000621517.1 link	c.-175G>A		upstream_gene_variant		2		ENSP00000484552.1		P36382
GJA5	ENST00000430508.1 link	c.-175G>A		upstream_gene_variant		2		ENSP00000407645.1		A0A0B4J1Y3

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28344

AN:

151872

Hom.:

3157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0586

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.109

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.174

AC:

AN:

224

Hom.:

Cov.:

AF XY:

0.169

AC XY:

AN XY:

142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AF:

0.167

AC:

AN:

Gnomad4 EAS exome

AF:

0.250

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.138

AC:

AN:

Gnomad4 NFE exome

AF:

0.202

AC:

AN:

Gnomad4 Remaining exome

AF:

0.200

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.187

AC:

28369

AN:

151990

Hom.:

3159

Cov.:

AF XY:

0.186

AC XY:

13805

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0590

AC:

0.0589568

AN:

0.0589568

Gnomad4 AMR

AF:

0.230

AC:

0.229827

AN:

0.229827

Gnomad4 ASJ

AF:

0.181

AC:

0.18098

AN:

0.18098

Gnomad4 EAS

AF:

0.334

AC:

0.333787

AN:

0.333787

Gnomad4 SAS

AF:

0.176

AC:

0.176007

AN:

0.176007

Gnomad4 FIN

AF:

0.230

AC:

0.230456

AN:

0.230456

Gnomad4 NFE

AF:

0.236

AC:

0.235994

AN:

0.235994

Gnomad4 OTH

AF:

0.205

AC:

0.205128

AN:

0.205128

Heterozygous variant carriers

1109

2217

3326

4434

5543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

187

Bravo

AF:

0.185

Asia WGS

AF:

0.246

AC:

854

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial atrial fibrillation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.85

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over