Genetic Variant LOC105374433:n.202+2209C>A (chr4-43318490-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_925266.3(LOC105374433):n.202+2209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,074 control chromosomes in the GnomAD database, including 22,002 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 0.52 ( 22002 hom., cov: 34)

Consequence

LOC105374433
XR_925266.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.308

Publications

0 publications found

Variant links:

Genes affected

LOC105374433 (HGNC:):

LOC105374433 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105374433	XR_925266.3 link	n.202+2209C>A	intron_variant	Intron 1 of 3
LOC105374433	XR_925267.3 link	n.202+2209C>A	intron_variant	Intron 1 of 2
LOC105374434	XR_925268.1 link	n.144-10452G>T	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78802

AN:

151956

Hom.:

22009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.760

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.645

Gnomad OTH

AF:

0.537

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

GnomAD4 genome

AF:

0.518

AC:

78801

AN:

152074

Hom.:

22002

Cov.:

AF XY:

0.509

AC XY:

37862

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.351

AC:

14560

AN:

41478

American (AMR)

AF:

0.500

AC:

7633

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1777

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

909

AN:

5184

South Asian (SAS)

AF:

0.456

AC:

2201

AN:

4824

European-Finnish (FIN)

AF:

0.556

AC:

5876

AN:

10562

Middle Eastern (MID)

AF:

0.596

AC:

174

AN:

292

European-Non Finnish (NFE)

AF:

0.645

AC:

43853

AN:

67978

Other (OTH)

AF:

0.533

AC:

1126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1887

3775

5662

7550

9437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.573

Hom.:

3406

Bravo

AF:

0.508

Asia WGS

AF:

0.314

AC:

1095

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.62

PhyloP100

-0.31

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over