9-5181467-C-T

Variant names:

• chr9-5181467-C-T
• rs7047795
• NM_007179.3:c.289+3847G>A

Variant summary

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

The NM_007179.3(INSL6):​c.289+3847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,766 control chromosomes in the GnomAD database, including 15,853 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 0.41 (15853 hom., cov: 31)
• Consequence: INSL6 NM_007179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 9 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSL6	NM_007179.3	c.289+3847G>A		intron_variant	Intron 1 of 1	ENST00000381641.4	NP_009110.2
INSL6	XM_011517702.4	c.289+3847G>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+3847G>A		intron_variant	Intron 1 of 1	1	NM_007179.3	ENSP00000371054.3
INSL6	ENST00000649639.1	c.289+3847G>A		intron_variant	Intron 1 of 3			ENSP00000497955.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62881 AN: 151648 Hom.: 15815 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.254

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: 0.375

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

GnomAD4 genome AF: 0.415 AC: 62977 AN: 151766 Hom.: 15853 Cov.: 31 AF XY: 0.413 AC XY: 30638 AN XY: 74158

African (AFR) AF: 0.722 AC: 29881 AN: 41402

American (AMR) AF: 0.353 AC: 5390 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1326 AN: 5174

South Asian (SAS) AF: 0.308 AC: 1478 AN: 4794

European-Finnish (FIN) AF: 0.343 AC: 3601 AN: 10496

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19298 AN: 67872

Other (OTH) AF: 0.376 AC: 791 AN: 2104

Alfa AF: 0.317 Hom.: 25328

Bravo AF: 0.424

Asia WGS AF: 0.329 AC: 1139 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.68
PhyloP100		-2.7
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: rs7047795; hg19: chr9-5181467; COSMIC: COSV67562719;