chr19-17820688-C-T

Variant names:

• chr19-17820688-C-T
• rs4808100
• NM_005543.4:c.190+629G>A

Variant summary

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

The NM_005543.4(INSL3):​c.190+629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,828 control chromosomes in the GnomAD database, including 10,313 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 0.36 (10313 hom., cov: 31)
• Consequence: INSL3 NM_005543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 10 publications found

Genes affected

INSL3 (HGNC:6086): (insulin like 3) This gene encodes a member of the insulin-like hormone superfamily. The encoded protein is mainly produced in gonadal tissues. Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female fertility. This protein may also act as a hormone to regulate growth and differentiation of gubernaculum, and thus mediating intra-abdominal testicular descent. Mutations in this gene may lead to cryptorchidism. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

INSL3 Gene-Disease associations (from GenCC):

• cryptorchidism

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSL3	NM_005543.4	c.190+629G>A		intron_variant	Intron 1 of 1	ENST00000317306.8	NP_005534.2
INSL3	NM_001265587.2	c.191-198G>A		intron_variant	Intron 1 of 2		NP_001252516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSL3	ENST00000317306.8	c.190+629G>A		intron_variant	Intron 1 of 1	1	NM_005543.4	ENSP00000321724.6
INSL3	ENST00000379695.5	c.191-198G>A		intron_variant	Intron 1 of 2	1		ENSP00000369017.4
INSL3	ENST00000598577.1	c.187+629G>A		intron_variant	Intron 1 of 1	1		ENSP00000469309.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54539 AN: 151710 Hom.: 10309 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.359 AC: 54573 AN: 151828 Hom.: 10313 Cov.: 31 AF XY: 0.356 AC XY: 26368 AN XY: 74162

African (AFR) AF: 0.386 AC: 15975 AN: 41402

American (AMR) AF: 0.316 AC: 4823 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3470

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5170

South Asian (SAS) AF: 0.169 AC: 812 AN: 4806

European-Finnish (FIN) AF: 0.422 AC: 4440 AN: 10520

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26129 AN: 67904

Other (OTH) AF: 0.357 AC: 754 AN: 2114

Alfa AF: 0.365 Hom.: 14136

Bravo AF: 0.352

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		0.30
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: rs4808100; hg19: chr19-17931497;