dbSNP rs2272719: DEFA5:p.Thr69Thr (chr8-7055509-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_021010.3(DEFA5):c.207C>T(p.Thr69Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,611,732 control chromosomes in the GnomAD database, including 110,914 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 0.32 ( 8673 hom., cov: 32)

Exomes 𝑓: 0.37 ( 102241 hom. )

Consequence

DEFA5
NM_021010.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.844

Variant links:

Genes affected

DEFA5 (HGNC:2764): (defensin alpha 5) 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 of the alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 5, is highly expressed in the secretory granules of Paneth cells of the ileum. [provided by RefSeq, Oct 2014]

DEFA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-0.844 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA5	NM_021010.3 link	c.207C>T	p.Thr69Thr	synonymous_variant	Exon 2 of 2	ENST00000330590.4	NP_066290.1	Q01523

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA5	ENST00000330590.4 link	c.207C>T	p.Thr69Thr	synonymous_variant	Exon 2 of 2	1	NM_021010.3	ENSP00000329890.2		Q01523

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49359

AN:

151848

Hom.:

8673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.332

GnomAD3 exomes

AF:

0.360

AC:

89477

AN:

248888

Hom.:

16476

AF XY:

0.363

AC XY:

48781

AN XY:

134510

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.294

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.371

AC:

542050

AN:

1459766

Hom.:

102241

Cov.:

AF XY:

0.372

AC XY:

270024

AN XY:

726098

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.360

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.325

AC:

49383

AN:

151966

Hom.:

8673

Cov.:

AF XY:

0.330

AC XY:

24503

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.334

Alfa

AF:

0.357

Hom.:

5925

Bravo

AF:

0.314

Asia WGS

AF:

0.333

AC:

1158

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.1

DANN

Benign

0.61

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over