rs17399591

Variant names:

• chr15-49421024-A-G
• rs17399591
• NM_152647.3:c.1013-49625T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-49421024-A-G
• chr15-49421024-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152647.3(FAM227B):​c.1013-49625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,290 control chromosomes in the GnomAD database, including 94 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 0.028 (94 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 1 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.028 (4264/152290) while in subpopulation NFE AF = 0.0407 (2768/68016). AF 95% confidence interval is 0.0394. There are 94 homozygotes in GnomAd4. There are 1959 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 94 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.1013-49625T>C		intron	N/A	NP_689860.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1013-49625T>C		intron	N/A	ENSP00000299338.6

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4268 AN: 152172 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00741

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0280 AC: 4264 AN: 152290 Hom.: 94 Cov.: 32 AF XY: 0.0263 AC XY: 1959 AN XY: 74462

African (AFR) AF: 0.00738 AC: 307 AN: 41572

American (AMR) AF: 0.0356 AC: 544 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4828

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10624

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0407 AC: 2768 AN: 68016

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0360 Hom.: 138

Bravo AF: 0.0291

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.72
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17399591; hg19: chr15-49713221;