rs2080727

Variant names:

• chr2-24128037-A-G
• rs2080727
• NM_001145710.2:c.99+3577A>G

Variant summary

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

The NM_001145710.2(FAM228B):​c.99+3577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,920 control chromosomes in the GnomAD database, including 7,808 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 0.31 (7808 hom., cov: 32)
• Consequence: FAM228B NM_001145710.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 8 publications found

Genes affected

FAM228B (HGNC:24736): (family with sequence similarity 228 member B)

ENSG00000276087 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM228B	NM_001145710.2	c.99+3577A>G		intron_variant	Intron 2 of 10	ENST00000615575.5	NP_001139182.1
FAM228B	NM_001291328.2	c.-120-7082A>G		intron_variant	Intron 3 of 10		NP_001278257.1
FAM228B	NR_111929.2	n.304-7082A>G		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM228B	ENST00000615575.5	c.99+3577A>G		intron_variant	Intron 2 of 10	5	NM_001145710.2	ENSP00000482482.1
ENSG00000276087	ENST00000610442.1	n.6+3577A>G		intron_variant	Intron 1 of 13	2		ENSP00000483650.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47503 AN: 151802 Hom.: 7807 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.313 AC: 47517 AN: 151920 Hom.: 7808 Cov.: 32 AF XY: 0.314 AC XY: 23318 AN XY: 74230

African (AFR) AF: 0.255 AC: 10563 AN: 41396

American (AMR) AF: 0.228 AC: 3485 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3472

East Asian (EAS) AF: 0.151 AC: 784 AN: 5180

South Asian (SAS) AF: 0.432 AC: 2081 AN: 4816

European-Finnish (FIN) AF: 0.380 AC: 4003 AN: 10526

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24346 AN: 67958

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.346 Hom.: 4400

Bravo AF: 0.296

Asia WGS AF: 0.263 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.26
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2080727; hg19: chr2-24350907;