rs527665020

Variant names:

• chr15-56920030-TTTTGTTTG-T
• rs527665020
• NM_207037.2:c.75+58_75+65delGTTTGTTT

Your query was ambiguous. Multiple possible variants found:

• chr15-56920030-TTTTGTTTG-T
• chr15-56920030-TTTTGTTTG-TTTTG
• chr15-56920030-TTTTGTTTG-TTTTGTTTGTTTG
• chr15-56920030-TTTTGTTTG-TTTTGTTTGTTTGTTTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_207037.2(TCF12):​c.75+58_75+65delGTTTGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,605,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

Genes affected

TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

TCF12 Gene-Disease associations (from GenCC):

• TCF12-related craniosynostosis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• hypogonadotropic hypogonadism 26 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Kallmann syndrome

  Inheritance: AR, AD Classification: STRONG Submitted by: Franklin by Genoox
• isolated brachycephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated plagiocephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00118 (180/151940) while in subpopulation AFR AF = 0.00417 (173/41446). AF 95% confidence interval is 0.00367. There are 0 homozygotes in GnomAd4. There are 87 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207037.2. 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
	TCF12	NM_207037.2	MANE Select	c.75+58_75+65delGTTTGTTT		intron	N/A	NP_996920.1	Q99081-3
	TCF12	NM_001322151.2		c.75+58_75+65delGTTTGTTT		intron	N/A	NP_001309080.1	Q99081-3
	TCF12	NM_001322159.3		c.75+58_75+65delGTTTGTTT		intron	N/A	NP_001309088.1	Q99081-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF12	ENST00000333725.10	TSL:1 MANE Select	c.75+43_75+50delTTTGTTTG		intron	N/A	ENSP00000331057.6	Q99081-3
	TCF12	ENST00000267811.9	TSL:1	c.75+43_75+50delTTTGTTTG		intron	N/A	ENSP00000267811.5	Q99081-1
	TCF12	ENST00000557843.5	TSL:1	c.75+43_75+50delTTTGTTTG		intron	N/A	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 179 AN: 151822 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000324 AC: 80 AN: 246558 AF XY: 0.000233

Gnomad AFR exome AF: 0.00421

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000630

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000151 AC: 219 AN: 1453872 Hom.: 0 AF XY: 0.000142 AC XY: 103 AN XY: 723710

African (AFR) AF: 0.00417 AC: 139 AN: 33326

American (AMR) AF: 0.000157 AC: 7 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39624

South Asian (SAS) AF: 0.0000814 AC: 7 AN: 86030

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53214

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.0000344 AC: 38 AN: 1105276

Other (OTH) AF: 0.000399 AC: 24 AN: 60094

GnomAD4 genome AF: 0.00118 AC: 180 AN: 151940 Hom.: 0 Cov.: 30 AF XY: 0.00117 AC XY: 87 AN XY: 74252

African (AFR) AF: 0.00417 AC: 173 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67928

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs527665020; hg19: chr15-57212228;