rs12210179

Positions:

• chr6-22298817-T-C

Variant summary

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

The NM_001163558.3(PRL):​c.-97-1738A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,192 control chromosomes in the GnomAD database, including 3,157 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 0.19 (3157 hom., cov: 33)
• Consequence: PRL NM_001163558.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

Genes affected

PRL (HGNC:9445): (prolactin) This gene encodes the anterior pituitary hormone prolactin. This secreted hormone is a growth regulator for many tissues, including cells of the immune system. It may also play a role in cell survival by suppressing apoptosis, and it is essential for lactation. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

CASC15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRL	NM_001163558.3	c.-97-1738A>G		intron_variant			NP_001157030.1
PRL	XM_011514753.3	c.-97-1738A>G		intron_variant			XP_011513055.1
PRL	XM_011514754.3	c.-97-1738A>G		intron_variant			XP_011513056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000651757.1	c.-97-1738A>G		intron_variant				ENSP00000499154.1
PRL	ENST00000651245.1	c.-97-1738A>G		intron_variant				ENSP00000498773.1
CASC15	ENST00000561912.3	n.569+7829T>C		intron_variant		5
CASC15	ENST00000651569.1	n.505+7829T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28354 AN: 152074 Hom.: 3157 Cov.: 33

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.186 AC: 28348 AN: 152192 Hom.: 3157 Cov.: 33 AF XY: 0.182 AC XY: 13571 AN XY: 74394

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.178

Alfa AF: 0.237 Hom.: 6047

Bravo AF: 0.176

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12210179; hg19: chr6-22299046;