rs699699

Variant names:

• chr6-107621148-G-A
• rs699699
• NM_018013.4:c.670-12366G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-107621148-G-A
• chr6-107621148-G-C

Variant summary

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

The NM_018013.4(SOBP):​c.670-12366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 850,542 control chromosomes in the GnomAD database, including 414,078 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 0.98 (73019 hom., cov: 33)
  • Exomes 𝑓: 0.99 (341059 hom.)
• Consequence: SOBP NM_018013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655
• Publications: 1 publications found

Genes affected

SOBP (HGNC:29256): (sine oculis binding protein homolog) The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene have also been linked to intellectual disability. [provided by RefSeq, Mar 2011]

SOBP Gene-Disease associations (from GenCC):

• intellectual disability, anterior maxillary protrusion, and strabismus

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• syndromic intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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 (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4	c.670-12366G>A		intron_variant	Intron 5 of 6	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10	c.670-12366G>A		intron_variant	Intron 5 of 6	5	NM_018013.4	ENSP00000318900.5

Frequencies

GnomAD3 genomes AF: 0.979 AC: 149018 AN: 152238 Hom.: 72960 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.968

GnomAD4 exome AF: 0.988 AC: 690049 AN: 698186 Hom.: 341059 Cov.: 8 AF XY: 0.988 AC XY: 320803 AN XY: 324582

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

African (AFR) AF: 0.952 AC: 12518 AN: 13150

American (AMR) AF: 0.983 AC: 792 AN: 806

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 4244 AN: 4378

East Asian (EAS) AF: 1.00 AC: 2998 AN: 2998

South Asian (SAS) AF: 0.993 AC: 13467 AN: 13566

European-Finnish (FIN) AF: 0.996 AC: 231 AN: 232

Middle Eastern (MID) AF: 0.955 AC: 1297 AN: 1358

European-Non Finnish (NFE) AF: 0.989 AC: 632132 AN: 638990

Other (OTH) AF: 0.985 AC: 22370 AN: 22708

⚠️ 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: 0.979 AC: 149136 AN: 152356 Hom.: 73019 Cov.: 33 AF XY: 0.980 AC XY: 73035 AN XY: 74506

African (AFR) AF: 0.955 AC: 39688 AN: 41554

American (AMR) AF: 0.978 AC: 14966 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3378 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5193 AN: 5194

South Asian (SAS) AF: 0.993 AC: 4794 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10628

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67250 AN: 68048

Other (OTH) AF: 0.969 AC: 2050 AN: 2116

Alfa AF: 0.978 Hom.: 39393

Bravo AF: 0.976

Asia WGS AF: 0.993 AC: 3453 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	12
DANN	Benign	0.74
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs699699; hg19: chr6-107942352;