rs143039347

Variant names:

• chr19-7669318-G-A
• rs143039347
• NM_020415.4:c.-9G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-7669318-G-A
• chr19-7669318-G-C
• chr19-7669318-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020415.4(RETN):​c.-9G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000733 in 1,604,112 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 30)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: RETN NM_020415.4 splice_region
• Scores: Splicing: ADA: 0.001187
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 1 publications found

Genes affected

RETN (HGNC:20389): (resistin) This gene belongs to the family defined by the mouse resistin-like genes. The characteristic feature of this family is the C-terminal stretch of 10 cys residues with identical spacing. The mouse homolog of this protein is secreted by adipocytes, and may be the hormone potentially linking obesity to type II diabetes. The encoded protein also has an antimicrobial role in skin, displaying antibacterial activity against both Gram positive and Gram negative bacteria. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2020]

RETN Gene-Disease associations (from GenCC):

• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAd4 at 567 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020415.4. 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
	RETN	NM_020415.4	MANE Select	c.-9G>A		splice_region	Exon 2 of 4	NP_065148.1	Q9HD89-1
	RETN	NM_020415.4	MANE Select	c.-9G>A		5_prime_UTR	Exon 2 of 4	NP_065148.1	Q9HD89-1
	RETN	NM_001385726.1		c.-9G>A		splice_region	Exon 2 of 4	NP_001372655.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETN	ENST00000221515.6	TSL:1 MANE Select	c.-9G>A		splice_region	Exon 2 of 4	ENSP00000221515.1	Q9HD89-1
	RETN	ENST00000221515.6	TSL:1 MANE Select	c.-9G>A		5_prime_UTR	Exon 2 of 4	ENSP00000221515.1	Q9HD89-1
	RETN	ENST00000629642.1	TSL:5	c.-9G>A		splice_region	Exon 2 of 3	ENSP00000485998.1	Q9HD89-2

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 568 AN: 152052 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.000994 AC: 250 AN: 251418 AF XY: 0.000787

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000419 AC: 609 AN: 1451942 Hom.: 2 Cov.: 28 AF XY: 0.000368 AC XY: 266 AN XY: 722978

African (AFR) AF: 0.0141 AC: 471 AN: 33290

American (AMR) AF: 0.000604 AC: 27 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86064

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53398

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5750

European-Non Finnish (NFE) AF: 0.0000363 AC: 40 AN: 1102952

Other (OTH) AF: 0.000732 AC: 44 AN: 60082

GnomAD4 genome AF: 0.00373 AC: 567 AN: 152170 Hom.: 4 Cov.: 30 AF XY: 0.00351 AC XY: 261 AN XY: 74390

African (AFR) AF: 0.0129 AC: 535 AN: 41516

American (AMR) AF: 0.00144 AC: 22 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.00371

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.72
PhyloP100		-2.3
PromoterAI		-0.068	Neutral
Mutation Taster		=296/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
SpliceAI score (max)		0.010		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: rs143039347; hg19: chr19-7734204;