Genetic Variant APOM:c.-103+192T>G (chr6-31652743-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001256169.2(APOM):c.-103+192T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 153,158 control chromosomes in the GnomAD database, including 513 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 0.069 ( 508 hom., cov: 32)

Exomes 𝑓: 0.054 ( 5 hom. )

Consequence

APOM
NM_001256169.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

Publications

134 publications found

Variant links:

COSMIC-nc: COSV52990728

Genes affected

APOM (HGNC:13916): (apolipoprotein M) The protein encoded by this gene is an apolipoprotein and member of the lipocalin protein family. It is found associated with high density lipoproteins and to a lesser extent with low density lipoproteins and triglyceride-rich lipoproteins. The encoded protein is secreted through the plasma membrane but remains membrane-bound, where it is involved in lipid transport. Alternate splicing results in both coding and non-coding variants of this gene. [provided by RefSeq, Jan 2012]

APOM links:

BAG6 (HGNC:13919): (BAG cochaperone 6) This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BAG6 links:

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new If you want to explore the variant's impact on the transcript NM_001256169.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256169.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOM	NM_001256169.2		c.-103+192T>G	intron	N/A	NP_001243098.1	O95445-2
APOM	NR_045828.2		n.148+192T>G	intron	N/A
BAG6	NM_001387994.1	MANE Select	c.-333A>C	upstream_gene	N/A	NP_001374923.1	P46379-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOM	ENST00000375920.8	TSL:1	c.-103+192T>G	intron	N/A	ENSP00000365085.4	O95445-2
BAG6	ENST00000888810.1		c.-333A>C	5_prime_UTR	Exon 1 of 25	ENSP00000558869.1
APOM	ENST00000375918.6	TSL:2	c.-103+192T>G	intron	N/A	ENSP00000365083.2	Q5SRP5

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10559

AN:

152098

Hom.:

508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0316

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0784

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0516

GnomAD4 exome

AF:

0.0541

AC:

AN:

942

Hom.:

Cov.:

AF XY:

0.0529

AC XY:

AN XY:

586

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0893

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0712

AC:

AN:

576

Other (OTH)

AF:

0.0641

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0694

AC:

10558

AN:

152216

Hom.:

508

Cov.:

AF XY:

0.0647

AC XY:

4818

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0387

AC:

1608

AN:

41556

American (AMR)

AF:

0.0315

AC:

482

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0397

AC:

138

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0784

AC:

831

AN:

10596

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7321

AN:

67992

Other (OTH)

AF:

0.0511

AC:

108

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

511

1022

1533

2044

2555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0966

Hom.:

2837

Bravo

AF:

0.0650

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.9

(source)

DANN

Benign

0.77

PhyloP100

-0.027

PromoterAI

-0.0094

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over