9-5182159-C-T

Variant names:

• chr9-5182159-C-T
• rs10974993
• NM_007179.3:c.289+3155G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007179.3(INSL6):​c.289+3155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,794 control chromosomes in the GnomAD database, including 12,365 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 0.38 (12365 hom., cov: 31)
• Consequence: INSL6 NM_007179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

Genes affected

INSL6 (HGNC:6089): (insulin like 6) The protein encoded by this gene contains a classical signature of the insulin superfamily and is significantly similar to relaxin and relaxin-like factor. This gene is preferentially expressed in testis. Its expression in testis is restricted to interstitial cells surrounding seminiferous tubules, which suggests a role in sperm development and fertilization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSL6	NM_007179.3	c.289+3155G>A		intron_variant	Intron 1 of 1	ENST00000381641.4	NP_009110.2
INSL6	XM_011517702.4	c.289+3155G>A		intron_variant	Intron 1 of 2		XP_011516004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSL6	ENST00000381641.4	c.289+3155G>A		intron_variant	Intron 1 of 1	1	NM_007179.3	ENSP00000371054.3
INSL6	ENST00000649639.1	c.289+3155G>A		intron_variant	Intron 1 of 3			ENSP00000497955.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57501 AN: 151676 Hom.: 12344 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.379 AC: 57566 AN: 151794 Hom.: 12365 Cov.: 31 AF XY: 0.379 AC XY: 28104 AN XY: 74176

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.349

Alfa AF: 0.282 Hom.: 2764

Bravo AF: 0.384

Asia WGS AF: 0.321 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs10974993; hg19: chr9-5182159; COSMIC: COSV67562729;