6-22292324-G-A

Position:

• chr6-22292324-G-A

Variant summary

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

The NM_000948.6(PRL):​c.312+214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,080 control chromosomes in the GnomAD database, including 3,389 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 0.20 (3389 hom., cov: 33)
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRL	NM_000948.6	c.312+214C>T		intron_variant		ENST00000306482.2	NP_000939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2	c.312+214C>T		intron_variant		1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31160 AN: 151962 Hom.: 3387 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.00692

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.205 AC: 31175 AN: 152080 Hom.: 3389 Cov.: 33 AF XY: 0.200 AC XY: 14847 AN XY: 74344

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.00693

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.189

Alfa AF: 0.223 Hom.: 1830

Bravo AF: 0.198

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7739889; hg19: chr6-22292553; COSMIC: COSV60593892;