Genetic Variant NM_021982.3:c.2266+30G>A (chr5-134698087-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021982.3(SEC24A):c.2266+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,572,916 control chromosomes in the GnomAD database, including 739,538 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 0.98 ( 72844 hom., cov: 29)

Exomes 𝑓: 0.97 ( 666694 hom. )

Consequence

SEC24A
NM_021982.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.403

Publications

7 publications found

Variant links:

Genes affected

SEC24A (HGNC:10703): (SEC24 homolog A, COPII coat complex component) The protein encoded by this gene belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

SEC24A links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24A	NM_021982.3 link	c.2266+30G>A		intron_variant	Intron 15 of 22	ENST00000398844.7	NP_068817.1	O95486-1B4E205

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24A	ENST00000398844.7 link	c.2266+30G>A		intron_variant	Intron 15 of 22	2	NM_021982.3	ENSP00000381823.2		O95486-1

Frequencies

GnomAD3 genomes

AF:

0.978

AC:

148730

AN:

152030

Hom.:

72781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.990

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.981

Gnomad FIN

AF:

0.973

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.965

Gnomad OTH

AF:

0.983

GnomAD2 exomes

AF:

0.977

AC:

220095

AN:

225330

AF XY:

0.976

show subpopulations

Gnomad AFR exome

AF:

0.994

Gnomad AMR exome

AF:

0.990

Gnomad ASJ exome

AF:

0.974

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.975

Gnomad NFE exome

AF:

0.967

Gnomad OTH exome

AF:

0.978

GnomAD4 exome

AF:

0.969

AC:

1376251

AN:

1420768

Hom.:

666694

Cov.:

AF XY:

0.969

AC XY:

685581

AN XY:

707524

show subpopulations

African (AFR)

AF:

0.995

AC:

31561

AN:

31710

American (AMR)

AF:

0.990

AC:

37849

AN:

38246

Ashkenazi Jewish (ASJ)

AF:

0.974

AC:

24266

AN:

24906

East Asian (EAS)

AF:

1.00

AC:

39465

AN:

39468

South Asian (SAS)

AF:

0.981

AC:

79417

AN:

80994

European-Finnish (FIN)

AF:

0.977

AC:

49950

AN:

51148

Middle Eastern (MID)

AF:

0.978

AC:

5468

AN:

5590

European-Non Finnish (NFE)

AF:

0.964

AC:

1051049

AN:

1089822

Other (OTH)

AF:

0.972

AC:

57226

AN:

58884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1881

3762

5642

7523

9404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21208

42416

63624

84832

106040

<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:

0.978

AC:

148852

AN:

152148

Hom.:

72844

Cov.:

AF XY:

0.979

AC XY:

72803

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.994

AC:

41258

AN:

41526

American (AMR)

AF:

0.990

AC:

15076

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

3377

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5170

AN:

5170

South Asian (SAS)

AF:

0.982

AC:

4743

AN:

4830

European-Finnish (FIN)

AF:

0.973

AC:

10298

AN:

10586

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.965

AC:

65653

AN:

68012

Other (OTH)

AF:

0.983

AC:

2076

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

158

315

473

630

788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.970

Hom.:

35257

Bravo

AF:

0.980

Asia WGS

AF:

0.991

AC:

3447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.3

(source)

DANN

Benign

0.74

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over