chr17-28758546-A-G

Variant names:

• chr17-28758546-A-G
• rs2043031
• NM_001077498.3:c.1413T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001077498.3(FAM222B):​c.1413T>C​(p.Leu471Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,610,036 control chromosomes in the GnomAD database, including 35,829 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 (2883 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32946 hom.)
• Consequence: FAM222B NM_001077498.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 21 publications found

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077498.3. 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
	FAM222B	NM_001077498.3	MANE Select	c.1413T>C	p.Leu471Leu	synonymous	Exon 3 of 3	NP_001070966.1
	FAM222B	NM_001288631.2		c.1419T>C	p.Leu473Leu	synonymous	Exon 4 of 4	NP_001275560.1
	FAM222B	NM_001288632.2		c.1413T>C	p.Leu471Leu	synonymous	Exon 5 of 5	NP_001275561.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222B	ENST00000581407.6	TSL:1 MANE Select	c.1413T>C	p.Leu471Leu	synonymous	Exon 3 of 3	ENSP00000462419.1
	FAM222B	ENST00000582266.6	TSL:1	c.*1214T>C		3_prime_UTR	Exon 3 of 3	ENSP00000462534.1
	FAM222B	ENST00000452648.8	TSL:2	c.1413T>C	p.Leu471Leu	synonymous	Exon 3 of 3	ENSP00000413645.3

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28869 AN: 152052 Hom.: 2878 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.211 AC: 51640 AN: 244498 AF XY: 0.214

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.209 AC: 304464 AN: 1457868 Hom.: 32946 Cov.: 35 AF XY: 0.212 AC XY: 153782 AN XY: 725420

African (AFR) AF: 0.155 AC: 5197 AN: 33474

American (AMR) AF: 0.212 AC: 9488 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6291 AN: 26134

East Asian (EAS) AF: 0.251 AC: 9955 AN: 39698

South Asian (SAS) AF: 0.312 AC: 26889 AN: 86254

European-Finnish (FIN) AF: 0.186 AC: 9257 AN: 49658

Middle Eastern (MID) AF: 0.240 AC: 1383 AN: 5768

European-Non Finnish (NFE) AF: 0.201 AC: 223601 AN: 1111824

Other (OTH) AF: 0.206 AC: 12403 AN: 60344

GnomAD4 genome AF: 0.190 AC: 28882 AN: 152168 Hom.: 2883 Cov.: 32 AF XY: 0.190 AC XY: 14164 AN XY: 74384

African (AFR) AF: 0.147 AC: 6113 AN: 41524

American (AMR) AF: 0.217 AC: 3320 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 814 AN: 3472

East Asian (EAS) AF: 0.191 AC: 986 AN: 5162

South Asian (SAS) AF: 0.307 AC: 1485 AN: 4830

European-Finnish (FIN) AF: 0.187 AC: 1985 AN: 10590

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13508 AN: 67978

Other (OTH) AF: 0.193 AC: 409 AN: 2114

Alfa AF: 0.198 Hom.: 6118

Bravo AF: 0.189

Asia WGS AF: 0.250 AC: 870 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.37
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: rs2043031; hg19: chr17-27085564; COSMIC: COSV57930323; COSMIC: COSV57930323;