rs2738120

Positions:

• chr8-6925114-G-C
• chr8-6925114-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001926.4(DEFA6):​c.194-187C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,126 control chromosomes in the GnomAD database, including 27,144 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 0.58 (27144 hom., cov: 33)
• Consequence: DEFA6 NM_001926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

Genes affected

DEFA6 (HGNC:2765): (defensin alpha 6) 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 appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 6, is highly expressed in the secretory granules of Paneth cells of the small intestine, and likely plays a role in host defense of human bowel. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFA6	NM_001926.4	c.194-187C>G		intron_variant		ENST00000297436.3	NP_001917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFA6	ENST00000297436.3	c.194-187C>G		intron_variant		1	NM_001926.4	ENSP00000297436.2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88113 AN: 152008 Hom.: 27149 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 88148 AN: 152126 Hom.: 27144 Cov.: 33 AF XY: 0.575 AC XY: 42774 AN XY: 74376

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.574

Alfa AF: 0.568 Hom.: 1993

Bravo AF: 0.551

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs2738120; hg19: chr8-6782636;