14-93246298-TAAA-T

Variant names:

• chr14-93246298-TAAA-T
• rs55659625
• NM_001002860.4:c.2122-15_2122-13delTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001002860.4(BTBD7):​c.2122-15_2122-13delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,328,896 control chromosomes in the GnomAD database, including 99 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (16 hom., cov: 0)
  • Exomes 𝑓: 0.032 (83 hom.)
• Consequence: BTBD7 NM_001002860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

BTBD7 (HGNC:18269): (BTB domain containing 7) Predicted to be involved in regulation of branching involved in salivary gland morphogenesis. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0146 (2088/142646) while in subpopulation SAS AF = 0.0237 (107/4524). AF 95% confidence interval is 0.0211. There are 16 homozygotes in GnomAd4. There are 979 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTBD7	NM_001002860.4	c.2122-15_2122-13delTTT		intron_variant	Intron 9 of 10	ENST00000334746.10	NP_001002860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD7	ENST00000334746.10	c.2122-15_2122-13delTTT		intron_variant	Intron 9 of 10	1	NM_001002860.4	ENSP00000335615.5
BTBD7	ENST00000554565.5	c.1069-15_1069-13delTTT		intron_variant	Intron 7 of 8	1		ENSP00000451010.1
BTBD7	ENST00000553975.1	c.967-15_967-13delTTT		intron_variant	Intron 5 of 6	2		ENSP00000450778.1
BTBD7	ENST00000355125.3	n.*743-15_*743-13delTTT		intron_variant	Intron 6 of 7	2		ENSP00000347246.3

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2085 AN: 142564 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.00428

Gnomad AMI AF: 0.00228

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0316

Gnomad EAS AF: 0.000405

Gnomad SAS AF: 0.0229

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.0367

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0112

GnomAD2 exomes AF: 0.0457 AC: 4944 AN: 108090 AF XY: 0.0463

Gnomad AFR exome AF: 0.0699

Gnomad AMR exome AF: 0.0333

Gnomad ASJ exome AF: 0.0664

Gnomad EAS exome AF: 0.0294

Gnomad FIN exome AF: 0.0280

Gnomad NFE exome AF: 0.0463

Gnomad OTH exome AF: 0.0528

GnomAD4 exome AF: 0.0321 AC: 38060 AN: 1186250 Hom.: 83 AF XY: 0.0329 AC XY: 18931 AN XY: 575406

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

African (AFR) AF: 0.0422 AC: 1063 AN: 25186

American (AMR) AF: 0.0263 AC: 560 AN: 21286

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 743 AN: 16734

East Asian (EAS) AF: 0.0145 AC: 485 AN: 33474

South Asian (SAS) AF: 0.0597 AC: 2744 AN: 45982

European-Finnish (FIN) AF: 0.0240 AC: 951 AN: 39646

Middle Eastern (MID) AF: 0.0520 AC: 239 AN: 4598

European-Non Finnish (NFE) AF: 0.0311 AC: 29614 AN: 950790

Other (OTH) AF: 0.0342 AC: 1661 AN: 48554

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0146 AC: 2088 AN: 142646 Hom.: 16 Cov.: 0 AF XY: 0.0141 AC XY: 979 AN XY: 69254

African (AFR) AF: 0.00432 AC: 169 AN: 39144

American (AMR) AF: 0.0105 AC: 150 AN: 14302

Ashkenazi Jewish (ASJ) AF: 0.0316 AC: 104 AN: 3294

East Asian (EAS) AF: 0.000406 AC: 2 AN: 4926

South Asian (SAS) AF: 0.0237 AC: 107 AN: 4524

European-Finnish (FIN) AF: 0.0111 AC: 98 AN: 8864

Middle Eastern (MID) AF: 0.0365 AC: 10 AN: 274

European-Non Finnish (NFE) AF: 0.0221 AC: 1424 AN: 64450

Other (OTH) AF: 0.0110 AC: 22 AN: 1992

Alfa AF: 0.0125 Hom.: 84

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55659625; hg19: chr14-93712644;