6-31377819-G-A

Variant names:

• chr6-31377819-G-A
• rs2507984
• ENST00000449999.1:n.401G>A

Variant summary

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

The ENST00000449999.1(FGFR3P1):​n.401G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 157,518 control chromosomes in the GnomAD database, including 5,023 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 0.23 (4980 hom., cov: 32)
  • Exomes 𝑓: 0.12 (43 hom.)
• Consequence: FGFR3P1 ENST00000449999.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 14 publications found

Genes affected

FGFR3P1 (HGNC:21664): (fibroblast growth factor receptor 3 pseudogene 1)

ENSG00000298426 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR3P1		n.31377819G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR3P1	ENST00000449999.1	n.401G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000298426	ENST00000755446.1	n.327-4161G>A		intron_variant	Intron 1 of 1
ENSG00000298474	ENST00000755731.1	n.303+420C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35096 AN: 151972 Hom.: 4979 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.119 AC: 648 AN: 5428 Hom.: 43 Cov.: 0 AF XY: 0.123 AC XY: 329 AN XY: 2684

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

African (AFR) AF: 0.0417 AC: 1 AN: 24

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.167 AC: 2 AN: 12

South Asian (SAS) AF: 0.104 AC: 65 AN: 624

European-Finnish (FIN) AF: 0.113 AC: 476 AN: 4196

Middle Eastern (MID) AF: 0.0556 AC: 9 AN: 162

European-Non Finnish (NFE) AF: 0.256 AC: 87 AN: 340

Other (OTH) AF: 0.113 AC: 7 AN: 62

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.231 AC: 35113 AN: 152090 Hom.: 4980 Cov.: 32 AF XY: 0.223 AC XY: 16616 AN XY: 74348

African (AFR) AF: 0.104 AC: 4308 AN: 41516

American (AMR) AF: 0.141 AC: 2164 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5164

South Asian (SAS) AF: 0.140 AC: 673 AN: 4816

European-Finnish (FIN) AF: 0.287 AC: 3031 AN: 10570

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22585 AN: 67934

Other (OTH) AF: 0.190 AC: 403 AN: 2116

Alfa AF: 0.293 Hom.: 17171

Bravo AF: 0.213

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	13
DANN	Benign	0.61
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2507984; hg19: chr6-31345596;