15-49533326-T-C

Variant names:

• chr15-49533326-T-C
• rs1354920
• NM_152647.3:c.874+8354A>G

Variant summary

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

The NM_152647.3(FAM227B):​c.874+8354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 151,730 control chromosomes in the GnomAD database, including 35,948 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 0.68 (35948 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 3 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=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.874+8354A>G		intron	N/A	NP_689860.2	Q96M60-1
	FAM227B	NM_001330293.2		c.772+8354A>G		intron	N/A	NP_001317222.1	Q96M60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.874+8354A>G		intron	N/A	ENSP00000299338.6	Q96M60-1
	FAM227B	ENST00000561064.5	TSL:1	c.772+8354A>G		intron	N/A	ENSP00000453028.1	Q96M60-2
	FAM227B	ENST00000968444.1		c.631+8354A>G		intron	N/A	ENSP00000638503.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103790 AN: 151612 Hom.: 35925 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.684 AC: 103855 AN: 151730 Hom.: 35948 Cov.: 31 AF XY: 0.684 AC XY: 50739 AN XY: 74140

African (AFR) AF: 0.578 AC: 23944 AN: 41398

American (AMR) AF: 0.766 AC: 11644 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2508 AN: 3464

East Asian (EAS) AF: 0.925 AC: 4783 AN: 5172

South Asian (SAS) AF: 0.680 AC: 3281 AN: 4822

European-Finnish (FIN) AF: 0.659 AC: 6945 AN: 10532

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48398 AN: 67848

Other (OTH) AF: 0.687 AC: 1442 AN: 2098

Alfa AF: 0.690 Hom.: 11176

Bravo AF: 0.692

Asia WGS AF: 0.745 AC: 2595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.38
PhyloP100		-3.0
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: rs1354920; hg19: chr15-49825523;