chr19-17818178-A-G

Variant names:

• chr19-17818178-A-G
• rs10421916
• NM_005543.4:c.191-1119T>C

Variant summary

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

The NM_005543.4(INSL3):​c.191-1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,878 control chromosomes in the GnomAD database, including 36,574 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 0.69 (36574 hom., cov: 30)
• Consequence: INSL3 NM_005543.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005543.4. 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
	INSL3	NM_005543.4	MANE Select	c.191-1119T>C		intron	N/A	NP_005534.2
	INSL3	NM_001265587.2		c.286-1119T>C		intron	N/A	NP_001252516.1	P51460-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSL3	ENST00000317306.8	TSL:1 MANE Select	c.191-1119T>C		intron	N/A	ENSP00000321724.6	P51460-1
	INSL3	ENST00000379695.5	TSL:1	c.286-1119T>C		intron	N/A	ENSP00000369017.4	P51460-2
	INSL3	ENST00000598577.1	TSL:1	c.188-1097T>C		intron	N/A	ENSP00000469309.1	M0QXQ3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104768 AN: 151760 Hom.: 36527 Cov.: 30

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.690 AC: 104864 AN: 151878 Hom.: 36574 Cov.: 30 AF XY: 0.692 AC XY: 51338 AN XY: 74222

African (AFR) AF: 0.791 AC: 32804 AN: 41456

American (AMR) AF: 0.636 AC: 9685 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3218 AN: 5112

South Asian (SAS) AF: 0.634 AC: 3054 AN: 4818

European-Finnish (FIN) AF: 0.728 AC: 7689 AN: 10566

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44206 AN: 67924

Other (OTH) AF: 0.647 AC: 1362 AN: 2106

Alfa AF: 0.662 Hom.: 23077

Bravo AF: 0.687

Asia WGS AF: 0.610 AC: 2123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-1.4
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: rs10421916; hg19: chr19-17928987;