rs2272719

Variant names:

• chr8-7055509-G-A
• rs2272719
• NM_021010.3:c.207C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-7055509-G-A
• chr8-7055509-G-C
• chr8-7055509-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.207C>T	p.Thr69Thr	synonymous_variant	Exon 2 of 2	ENST00000330590.4	NP_066290.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49359 AN: 151848 Hom.: 8673 Cov.: 32

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

GnomAD2 exomes AF: 0.360 AC: 89477 AN: 248888 AF XY: 0.363

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 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.: 37 AF XY: 0.372 AC XY: 270024 AN XY: 726098

African (AFR) AF: 0.169 AC: 5652 AN: 33466

American (AMR) AF: 0.349 AC: 15540 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 10228 AN: 26112

East Asian (EAS) AF: 0.297 AC: 11767 AN: 39668

South Asian (SAS) AF: 0.360 AC: 30942 AN: 86056

European-Finnish (FIN) AF: 0.409 AC: 21811 AN: 53270

Middle Eastern (MID) AF: 0.331 AC: 1911 AN: 5766

European-Non Finnish (NFE) AF: 0.381 AC: 422710 AN: 1110562

Other (OTH) AF: 0.356 AC: 21489 AN: 60302

GnomAD4 genome AF: 0.325 AC: 49383 AN: 151966 Hom.: 8673 Cov.: 32 AF XY: 0.330 AC XY: 24503 AN XY: 74268

African (AFR) AF: 0.182 AC: 7557 AN: 41458

American (AMR) AF: 0.360 AC: 5498 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1440 AN: 5156

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4814

European-Finnish (FIN) AF: 0.409 AC: 4316 AN: 10548

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26082 AN: 67932

Other (OTH) AF: 0.334 AC: 703 AN: 2102

Alfa AF: 0.346 Hom.: 7428

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
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272719; hg19: chr8-6913031; COSMIC: COSV57961877;