rs12210179

Variant names:

• chr6-22298817-T-C
• rs12210179
• NM_001163558.3:c.-97-1738A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRL	NM_001163558.3	c.-97-1738A>G		intron_variant	Intron 1 of 5		NP_001157030.1
PRL	XM_011514753.3	c.-97-1738A>G		intron_variant	Intron 1 of 5		XP_011513055.1
PRL	XM_011514754.3	c.-97-1738A>G		intron_variant	Intron 2 of 6		XP_011513056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000651757.1	c.-97-1738A>G		intron_variant	Intron 1 of 4			ENSP00000499154.1
PRL	ENST00000651245.1	c.-97-1738A>G		intron_variant	Intron 1 of 4			ENSP00000498773.1
CASC15	ENST00000561912.3	n.569+7829T>C		intron_variant	Intron 4 of 10	5
CASC15	ENST00000651569.1	n.505+7829T>C		intron_variant	Intron 4 of 7

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

African (AFR) AF: 0.0839 AC: 3484 AN: 41544

American (AMR) AF: 0.157 AC: 2404 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3470

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5186

South Asian (SAS) AF: 0.192 AC: 924 AN: 4818

European-Finnish (FIN) AF: 0.234 AC: 2476 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17391 AN: 67996

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.231 Hom.: 7335

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
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs12210179; hg19: chr6-22299046;