6-22291138-C-T

Variant names:

• chr6-22291138-C-T
• rs849886
• NM_000948.6:c.313-785G>A

Variant summary

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

The NM_000948.6(PRL):​c.313-785G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,888 control chromosomes in the GnomAD database, including 13,846 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 (13846 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRL NM_000948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRL	NM_000948.6	c.313-785G>A		intron_variant	Intron 3 of 4	ENST00000306482.2	NP_000939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRL	ENST00000306482.2	c.313-785G>A		intron_variant	Intron 3 of 4	1	NM_000948.6	ENSP00000302150.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61732 AN: 151770 Hom.: 13848 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.462

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.407 AC: 61760 AN: 151888 Hom.: 13846 Cov.: 33 AF XY: 0.410 AC XY: 30402 AN XY: 74228

African (AFR) AF: 0.201 AC: 8303 AN: 41388

American (AMR) AF: 0.489 AC: 7459 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1764 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3313 AN: 5166

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4824

European-Finnish (FIN) AF: 0.398 AC: 4188 AN: 10518

Middle Eastern (MID) AF: 0.534 AC: 155 AN: 290

European-Non Finnish (NFE) AF: 0.488 AC: 33129 AN: 67948

Other (OTH) AF: 0.464 AC: 978 AN: 2108

Alfa AF: 0.464 Hom.: 67980

Bravo AF: 0.405

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.31
DANN	Benign	0.79
PhyloP100		-1.9
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: rs849886; hg19: chr6-22291367;