15-49422203-T-C

Variant names:

• chr15-49422203-T-C
• rs73398284
• NM_152647.3:c.1013-50804A>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.1013-50804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,108 control chromosomes in the GnomAD database, including 3,144 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 (3144 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.1013-50804A>G		intron	N/A	NP_689860.2
	FAM227B	NM_001330293.2		c.*507A>G		downstream_gene	N/A	NP_001317222.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1013-50804A>G		intron	N/A	ENSP00000299338.6
	FAM227B	ENST00000561064.5	TSL:1	c.*507A>G		downstream_gene	N/A	ENSP00000453028.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28849 AN: 150996 Hom.: 3145 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.00506

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.191 AC: 28855 AN: 151108 Hom.: 3144 Cov.: 31 AF XY: 0.192 AC XY: 14172 AN XY: 73740

African (AFR) AF: 0.112 AC: 4603 AN: 41230

American (AMR) AF: 0.176 AC: 2666 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 898 AN: 3456

East Asian (EAS) AF: 0.00527 AC: 27 AN: 5122

South Asian (SAS) AF: 0.176 AC: 823 AN: 4676

European-Finnish (FIN) AF: 0.283 AC: 2938 AN: 10382

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16215 AN: 67772

Other (OTH) AF: 0.201 AC: 422 AN: 2096

Alfa AF: 0.207 Hom.: 468

Bravo AF: 0.179

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.62
PhyloP100		-0.25
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: rs73398284; hg19: chr15-49714400;