16-69300977-CAAAA-CAAA

Variant names:

• chr16-69300977-CA-C
• rs34703750
• NM_006750.4:c.*65delA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006750.4(SNTB2):​c.*65delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 799,440 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: 29)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: SNTB2 NM_006750.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 1 publications found

Genes affected

SNTB2 (HGNC:11169): (syntrophin beta 2) Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in Duchenne Muscular Dystrophy patients and is present in reduced amounts in Becker Muscular Dystrophy patients. The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related proteins. This gene is a member of the syntrophin gene family, which contains at least two other structurally-related genes. [provided by RefSeq, Jul 2008]

ENSG00000260914 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.17) population. However there is too low homozygotes in high coverage region: (expected more than 1804, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006750.4. 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
	SNTB2	NM_006750.4	MANE Select	c.*65delA		3_prime_UTR	Exon 7 of 7	NP_006741.1	Q13425-1
	SNTB2	NR_172088.1		n.1777delA		non_coding_transcript_exon	Exon 8 of 8
	SNTB2	NR_172089.1		n.1678delA		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTB2	ENST00000336278.9	TSL:1 MANE Select	c.*65delA		3_prime_UTR	Exon 7 of 7	ENSP00000338191.4	Q13425-1
	ENSG00000260914	ENST00000570054.3	TSL:5	c.93+1215delA		intron	N/A	ENSP00000461295.3	I3L4J1
	SNTB2	ENST00000958019.1		c.*65delA		3_prime_UTR	Exon 7 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 175 AN: 142608 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.000299

Gnomad EAS AF: 0.000811

Gnomad SAS AF: 0.000442

Gnomad FIN AF: 0.00841

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000890

Gnomad OTH AF: 0.00103

GnomAD4 exome AF: 0.115 AC: 75786 AN: 656800 Hom.: 0 Cov.: 6 AF XY: 0.118 AC XY: 39779 AN XY: 336084

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

African (AFR) AF: 0.122 AC: 1799 AN: 14700

American (AMR) AF: 0.173 AC: 3325 AN: 19242

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 2113 AN: 15018

East Asian (EAS) AF: 0.175 AC: 3849 AN: 21994

South Asian (SAS) AF: 0.172 AC: 7881 AN: 45798

European-Finnish (FIN) AF: 0.131 AC: 4392 AN: 33560

Middle Eastern (MID) AF: 0.0649 AC: 225 AN: 3468

European-Non Finnish (NFE) AF: 0.103 AC: 48544 AN: 473098

Other (OTH) AF: 0.122 AC: 3658 AN: 29922

⚠️ 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: 0.00122 AC: 174 AN: 142640 Hom.: 0 Cov.: 29 AF XY: 0.00128 AC XY: 88 AN XY: 68974

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

African (AFR) AF: 0.000514 AC: 20 AN: 38920

American (AMR) AF: 0.00119 AC: 17 AN: 14256

Ashkenazi Jewish (ASJ) AF: 0.000299 AC: 1 AN: 3344

East Asian (EAS) AF: 0.000610 AC: 3 AN: 4922

South Asian (SAS) AF: 0.000444 AC: 2 AN: 4506

European-Finnish (FIN) AF: 0.00841 AC: 71 AN: 8438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000890 AC: 58 AN: 65154

Other (OTH) AF: 0.00103 AC: 2 AN: 1950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=100/0	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: rs34703750; hg19: chr16-69334880; COSMIC: COSV60348642;