8-6936592-G-C

Variant names:

• chr8-6936592-G-C
• rs2741680
• NM_001925.3:c.172+136C>G

Variant summary

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

The NM_001925.3(DEFA4):​c.172+136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 805,574 control chromosomes in the GnomAD database, including 14,261 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 0.14 (2012 hom., cov: 33)
  • Exomes 𝑓: 0.18 (12249 hom.)
• Consequence: DEFA4 NM_001925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 2 publications found

Genes affected

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001925.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	NM_001925.3	MANE Select	c.172+136C>G		intron	N/A	NP_001916.1	P12838

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	ENST00000297435.3	TSL:1 MANE Select	c.172+136C>G		intron	N/A	ENSP00000297435.2	P12838

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22036 AN: 151992 Hom.: 2014 Cov.: 33

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0972

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.184 AC: 119942 AN: 653464 Hom.: 12249 AF XY: 0.182 AC XY: 59845 AN XY: 329362

African (AFR) AF: 0.0427 AC: 668 AN: 15650

American (AMR) AF: 0.196 AC: 2909 AN: 14864

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 2610 AN: 13570

East Asian (EAS) AF: 0.111 AC: 3360 AN: 30172

South Asian (SAS) AF: 0.0742 AC: 2456 AN: 33096

European-Finnish (FIN) AF: 0.141 AC: 4853 AN: 34304

Middle Eastern (MID) AF: 0.184 AC: 654 AN: 3548

European-Non Finnish (NFE) AF: 0.203 AC: 96840 AN: 476538

Other (OTH) AF: 0.176 AC: 5592 AN: 31722

GnomAD4 genome AF: 0.145 AC: 22043 AN: 152110 Hom.: 2012 Cov.: 33 AF XY: 0.142 AC XY: 10554 AN XY: 74350

African (AFR) AF: 0.0437 AC: 1814 AN: 41536

American (AMR) AF: 0.201 AC: 3076 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3468

East Asian (EAS) AF: 0.0966 AC: 500 AN: 5174

South Asian (SAS) AF: 0.0785 AC: 376 AN: 4788

European-Finnish (FIN) AF: 0.144 AC: 1529 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13389 AN: 67966

Other (OTH) AF: 0.185 AC: 392 AN: 2114

Alfa AF: 0.0388 Hom.: 30

Bravo AF: 0.149

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2741680; hg19: chr8-6794114;