ENST00000734230.1:n.63-147T>C

Variant names:

• chr8-6935800-T-C
• rs2702867
• ENST00000734230.1:n.63-147T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 6 publications found

Genes affected

ENSG00000295941 (HGNC:):

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000734230.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	NM_001925.3	MANE Select	c.*220A>G		downstream_gene	N/A	NP_001916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000295941	ENST00000734230.1		n.63-147T>C		intron	N/A
	DEFA4	ENST00000297435.3	TSL:1 MANE Select	c.*220A>G		downstream_gene	N/A	ENSP00000297435.2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101521 AN: 151886 Hom.: 34303 Cov.: 32

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.: 5 AF XY: 0.645 AC XY: 130852 AN XY: 202834

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

GnomAD4 genome AF: 0.668 AC: 101592 AN: 152004 Hom.: 34323 Cov.: 32 AF XY: 0.662 AC XY: 49163 AN XY: 74280

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.45
PhyloP100		0.11
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2702867; hg19: chr8-6793322;