Genetic Variant NM_005543.4:c.191-30C>T (chr19-17817089-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005543.4(INSL3):c.191-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,598,660 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 64 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 53 hom. )

Consequence

INSL3
NM_005543.4 intron

Scores

Splicing: ADA: 0.00003076

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0580

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-17817089-G-A is Benign according to our data. Variant chr19-17817089-G-A is described in ClinVar as [Benign]. Clinvar id is 1249049.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSL3	NM_005543.4 link	c.191-30C>T		intron_variant	Intron 1 of 1	ENST00000317306.8	NP_005534.2	P51460-1
INSL3	NM_001265587.2 link	c.286-30C>T		intron_variant	Intron 2 of 2		NP_001252516.1	P51460-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
INSL3	ENST00000317306.8 link	c.191-30C>T	intron_variant	Intron 1 of 1	1	NM_005543.4	ENSP00000321724.6	P51460-1
INSL3	ENST00000379695.5 link	c.286-30C>T	intron_variant	Intron 2 of 2	1		ENSP00000369017.4	P51460-2
INSL3	ENST00000598577.1 link	c.188-8C>T	splice_region_variant, intron_variant	Intron 1 of 1	1		ENSP00000469309.1	M0QXQ3

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2101

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00370

AC:

842

AN:

227574

Hom.:

AF XY:

0.00248

AC XY:

307

AN XY:

123802

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000196

Gnomad OTH exome

AF:

0.00210

GnomAD4 exome

AF:

0.00143

AC:

2070

AN:

1446400

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

837

AN XY:

719446

show subpopulations

Gnomad4 AFR exome

AF:

0.0525

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.0139

AC:

2120

AN:

152260

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

989

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0494

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.8

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over