rs730570

Variant names:

• chr14-100676553-G-A
• rs730570
• ENST00000557546.2:n.161-5C>T

Variant summary

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

The ENST00000557546.2(ENSG00000258717):​n.161-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,896 control chromosomes in the GnomAD database, including 36,782 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 0.65 (36520 hom., cov: 31)
  • Exomes 𝑓: 0.73 (262 hom.)
• Consequence: ENSG00000258717 ENST00000557546.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 48 publications found

Genes affected

ENSG00000258717 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258717	ENST00000557546.2	n.161-5C>T		splice_region_variant, intron_variant	Intron 1 of 1	3
ENSG00000258717	ENST00000761489.1	n.255-5C>T		splice_region_variant, intron_variant	Intron 2 of 2
ENSG00000258717	ENST00000761490.1	n.361-5C>T		splice_region_variant, intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98248 AN: 151876 Hom.: 36527 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.733 AC: 661 AN: 902 Hom.: 262 Cov.: 0 AF XY: 0.732 AC XY: 376 AN XY: 514

African (AFR) AF: 0.300 AC: 6 AN: 20

American (AMR) AF: 0.700 AC: 7 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 13 AN: 16

East Asian (EAS) AF: 0.127 AC: 13 AN: 102

South Asian (SAS) AF: 0.583 AC: 7 AN: 12

European-Finnish (FIN) AF: 0.745 AC: 76 AN: 102

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.854 AC: 504 AN: 590

Other (OTH) AF: 0.688 AC: 33 AN: 48

GnomAD4 genome AF: 0.646 AC: 98246 AN: 151994 Hom.: 36520 Cov.: 31 AF XY: 0.636 AC XY: 47251 AN XY: 74284

African (AFR) AF: 0.329 AC: 13630 AN: 41422

American (AMR) AF: 0.549 AC: 8387 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2954 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1089 AN: 5154

South Asian (SAS) AF: 0.588 AC: 2829 AN: 4814

European-Finnish (FIN) AF: 0.776 AC: 8223 AN: 10590

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58651 AN: 67958

Other (OTH) AF: 0.679 AC: 1436 AN: 2114

Alfa AF: 0.772 Hom.: 130809

Bravo AF: 0.614

Asia WGS AF: 0.350 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs730570; hg19: chr14-101142890;