Genetic Variant ENSG00000295941:n.63-147T>C (chr8-6935800-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000734230.1(ENSG00000295941):n.63-147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 540,864 control chromosomes in the GnomAD database, including 116,434 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 0.67 ( 34323 hom., cov: 32)

Exomes 𝑓: 0.65 ( 82111 hom. )

Consequence

ENSG00000295941
ENST00000734230.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.107

Publications

6 publications found

Variant links:

Genes affected

ENSG00000295941 (HGNC:):

ENSG00000295941 links:

DEFA4 (HGNC:2763): (defensin alpha 4) Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several alpha defensin genes are clustered on chromosome 8. This gene differs from other genes of this family by an extra 83-base segment that is apparently the result of a recent duplication within the coding region. The protein encoded by this gene, defensin, alpha 4, is found in the neutrophils; it exhibits corticostatic activity and inhibits corticotropin stimulated corticosterone production. [provided by RefSeq, Oct 2014]

DEFA4 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA4	NM_001925.3 link	c.*220A>G		downstream_gene_variant		ENST00000297435.3	NP_001916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000295941	ENST00000734230.1 link	n.63-147T>C		intron_variant	Intron 1 of 1
DEFA4	ENST00000297435.3 link	c.*220A>G		downstream_gene_variant		1	NM_001925.3	ENSP00000297435.2

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101521

AN:

151886

Hom.:

34303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.804

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.687

GnomAD4 exome

AF:

0.646

AC:

251280

AN:

388860

Hom.:

82111

Cov.:

AF XY:

0.645

AC XY:

130852

AN XY:

202834

show subpopulations

African (AFR)

AF:

0.708

AC:

7799

AN:

11018

American (AMR)

AF:

0.525

AC:

7765

AN:

14792

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

8316

AN:

11646

East Asian (EAS)

AF:

0.588

AC:

14912

AN:

25358

South Asian (SAS)

AF:

0.614

AC:

21067

AN:

34290

European-Finnish (FIN)

AF:

0.608

AC:

14508

AN:

23866

Middle Eastern (MID)

AF:

0.687

AC:

1182

AN:

1720

European-Non Finnish (NFE)

AF:

0.660

AC:

161130

AN:

243958

Other (OTH)

AF:

0.657

AC:

14601

AN:

22212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3970

7940

11911

15881

19851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1130

2260

3390

4520

5650

<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:

0.668

AC:

101592

AN:

152004

Hom.:

34323

Cov.:

AF XY:

0.662

AC XY:

49163

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.714

AC:

29620

AN:

41464

American (AMR)

AF:

0.582

AC:

8884

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2524

AN:

3472

East Asian (EAS)

AF:

0.620

AC:

3201

AN:

5162

South Asian (SAS)

AF:

0.640

AC:

3071

AN:

4798

European-Finnish (FIN)

AF:

0.615

AC:

6483

AN:

10538

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.668

AC:

45385

AN:

67982

Other (OTH)

AF:

0.692

AC:

1464

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1735

3469

5204

6938

8673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.646

Hom.:

5923

Bravo

AF:

0.669

Asia WGS

AF:

0.645

AC:

2247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

6.7

(source)

DANN

Benign

0.45

PhyloP100

0.11

Mutation Taster

=99/1

polymorphism

(source)

Splicing

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