8-6925114-G-C

Variant names:

• chr8-6925114-G-C
• rs2738120
• NM_001926.4:c.194-187C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000295932 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001926.4. 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
	DEFA6	NM_001926.4	MANE Select	c.194-187C>G		intron	N/A	NP_001917.1	Q01524

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA6	ENST00000297436.3	TSL:1 MANE Select	c.194-187C>G		intron	N/A	ENSP00000297436.2	Q01524
	ENSG00000295932	ENST00000734108.1		n.366+1323G>C		intron	N/A

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

African (AFR) AF: 0.395 AC: 16395 AN: 41478

American (AMR) AF: 0.455 AC: 6955 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2380 AN: 3472

East Asian (EAS) AF: 0.417 AC: 2156 AN: 5168

South Asian (SAS) AF: 0.724 AC: 3490 AN: 4820

European-Finnish (FIN) AF: 0.656 AC: 6937 AN: 10572

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47780 AN: 68010

Other (OTH) AF: 0.574 AC: 1213 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.31
PhyloP100		0.092
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: rs2738120; hg19: chr8-6782636;