rs760425570

Variant names:

• chr9-77020166-C-A
• rs760425570
• NM_001013735.1:c.512C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-77020166-C-A
• chr9-77020166-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001013735.1(FOXB2):​c.512C>A​(p.Pro171Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P171L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXB2 NM_001013735.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990
• Publications: 0 publications found

Genes affected

FOXB2 (HGNC:23315): (forkhead box B2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17678544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013735.1. 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
	FOXB2	NM_001013735.1	MANE Select	c.512C>A	p.Pro171Gln	missense	Exon 1 of 1	NP_001013757.1	Q5VYV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXB2	ENST00000376708.1	TSL:6 MANE Select	c.512C>A	p.Pro171Gln	missense	Exon 1 of 1	ENSP00000365898.1	Q5VYV0
	FOXB2	ENST00000850987.1		c.512C>A	p.Pro171Gln	missense	Exon 1 of 1	ENSP00000521069.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150480 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000973 AC: 2 AN: 205570 AF XY: 0.00000872

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000656 AC: 7 AN: 1067002 Hom.: 0 Cov.: 16 AF XY: 0.00000732 AC XY: 4 AN XY: 546804

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26106

American (AMR) AF: 0.0000231 AC: 1 AN: 43270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23502

East Asian (EAS) AF: 0.00 AC: 0 AN: 37598

South Asian (SAS) AF: 0.00 AC: 0 AN: 77592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4586

European-Non Finnish (NFE) AF: 0.00000779 AC: 6 AN: 770150

Other (OTH) AF: 0.00 AC: 0 AN: 47716

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0159933), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150480 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73372

African (AFR) AF: 0.00 AC: 0 AN: 41070

American (AMR) AF: 0.00 AC: 0 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67264

Other (OTH) AF: 0.00 AC: 0 AN: 2062

ExAC AF: 0.0000178 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.99
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.060	N
REVEL	Benign	0.075
Sift	Benign	0.30	T
Sift4G	Benign	0.70	T
Polyphen		0.99	D
Vest4		0.29
MutPred		0.43		Loss of glycosylation at P171 (P = 2e-04)
MVP		0.55
ClinPred		0.23	T
GERP RS		0.41
Varity_R		0.17
gMVP		0.34
Mutation Taster		=94/6	polymorphism

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: rs760425570; hg19: chr9-79635082;